Cell Cycle Genes and Related Methods

ABSTRACT

Novel plant polysaccharide synthesis genes and polypeptides encoded by such genes are provided. These genes and polynucleotide sequences are useful regulating polysaccharide synthesis and plant phenotype. Moreover, these genes are useful for expression profiling of plant polysaccharide synthesis genes. The invention specifically provides cell cycle polynucleotide and polypeptide sequences isolated from  Eucalyptus  and  Pinus.

CROSS REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. provisional application Ser.No. 60/533,036, filed on Dec. 30, 2003, which is specificallyincorporated in its entirety herein by reference.

FIELD OF THE INVENTION

The present invention relates generally to the field of plant cell cyclegenes and polypeptides encoded by such genes, and the use of suchpolynucleotide and polypeptide sequences for regulating a plant cellcycle. The invention specifically provides cell cycle polynucleotide andpolypeptide sequences isolated from Eucalyptus and Pinus and sequencesrelated thereto.

BACKGROUND OF THE INVENTION

Cell growth and division are controlled by the temporal expression ofdifferent sets of genes, allowing the dividing cell to progress throughthe different phases of the cell cycle. Continued growth and organogesisin plants requires precise function of the cell cycle machinery. Plantdevelopment, which is directly affected by cell division rates andpatterns, also is influenced by environmental factors, such astemperature, nutrient availability, light, etc. See Gastal and Nelon,Plant Physiol. 105:191-7 (1994), Ben-Haj-Sahal and Tardieu, PlantPhysiol. 109:861-7 (1995), and Sacks et al., Plant Physiol. 114:519-27(1997). Plant development and phenotype are connected with the cellcycle, and altering expression of the genes involved in the cell cyclecan be a useful method of modifying plant development and altering plantphenotype.

The ability to alter expression of cell cycle genes is extremelypowerful because the cell cycle drives plant development, includinggrowth rates, responses to environmental cues, and resulting plantphenotype. Control of the plant cell cycle and phenotypes associatedwith alteration of cell cycle gene expression, in the vascular cambium,in particular, has applications for, inter alia, alteration of woodproperties and, in particular, lumber and wood pulp properties. Forexample, improvements to wood pulp that can be effected by altering cellcycle gene expression include increased or decreased lignin andcellulose content, and altered length, diameter, and lumen diameter ofcells. Manipulating the plant cell cycle, and in particular the cambiumcell cycle (i.e. the rate and angle of cell division), can also engineerbetter lumber having increased dimensional stability, increased tensilestrength, increased shear strength, increased compression strength,increased shock resistance, increased stiffness, increased or decreasedhardness, decreased spirality, decreased shrinkage, and desirablecharacteristics with respect to weight, density, and specific gravity.

A. Cell Cycle Genes and Proteins

1. Cyclin Dependent Protein Kinase

Progression through the cell cycle is regulated primarily bycyclin-dependent kinases (CDKs). CDKs are a conserved family ofeukaryotic serine/threonine protein kinases, which require heterodimerformation with a cyclin subunit for activity. For review see, e.g.Joubes et al., Plant Mol. Biol. 43: 607-20 (2000), Stals and Inze,Trends Plant Sci. 6:359-64 (2001), and John et al., Protoplasma 216:119-42 (2001).

The are five subclasses of CDK's, each having a different cyclin bindingconsensus sequence. In CDK type A the cyclin binding consensus sequenceis PSTAIRE. Id. The cyclin binding consensus sequence in CDK types B-1,B-2, and C are PPTTLRE, PPTALRE, and PITAIRE, respectively. Joubes etal, Plant Physiol, 126: 1403-15 (2001).

Cell cycle progression is directed, in part, by changes in CDK activity.CDK activity is modulated by a number of different cell cycle proteincomponents, such as changes in the abundance of individual cyclins dueto changing rates of biosynthesis and proteolysis. Fluctuations incyclin concentrations result in commensurate fluctuations in CDKactivity. Cyclin accumulation is especially important in terminating theG1 phase of the cell cycle because DNA replication is initiated by anincrease in CDK activity.

Activation of CDK also requires phosphorylation of a threonine residuewithin the T-loop of CDK by a CDK-activating kinase (CAK). Umeda et al.,Proc. Nat'l Acad. Sci. U.S.A. 97: 13396-400 (2000). It was suggested byYamaguchi et al., Plant J. 24: 11-20 (2000), that cyclin H is aregulatory subunit of CAK. CDK activity is further regulated byinteraction with a CDK regulatory subunit, a small (70-100 AA) proteininvolved in cell cycle regulation.

A cell must exit the cell cycle in order to commit to differentiation,senescence or apoptosis. This process involves the down-regulation ofCDK activities. CDK inhibitors (CKI) are low molecular weight proteins,which are important for cell cycle regulation and development. CKIs bindstoichiometrically to CDK and down-regulate the activity of CDKs.

Many biochemical properties of ICK1, the first plant CKI to beidentified from Arabidopsis thaliana, are known. Wang et al., Nature386:451-2 (1997) Wang et al., Plant J. 24: 613-23 (2000). ICK1 isexpressed at low levels in many tissue types, and there can be athreshold level of ICK1 that must be overcome before a cell can enterthe cell cycle. Wang et al., Plant J. 24: 613-23 (2000). ICK1 is inducedby the plant growth regulator abscisic acid (ABA), which inhibits celldivision by blocking DNA replication. When the expression of ICK1increases, there is a corresponding decrease in Cdc2-like H1 histoneactivity. ICK1 has been shown to bind in vitro with the cyclins C2c2aand CycD3, and deletion experiments have identified different domainregions for these two interactions.

Altering the expression of CDK regulatory protein or a subunit thereofis known to cause changes in plant phenotype. Overexpression of theArabidopsis CDK regulatory subunit, CKS1At, resulted in a reduction ofleaf size, root growth rates and meristem size. Additionally,overexpression of CKS1At resulted in inhibition of cell-cycleprogression, with an extension in the duration of the G1 and G2 phasesof the cell cycle.

2. Cyclins

Cyclins are positive regulatory subunits of cyclin-dependent kinase(CDK) enzymes and are required for CDK activity. Fowler et al., Mol.Biotech. 10, 123, 126. Cyclins and CDK complexes provide temporalregulation of transition through the cell cycle. Evidence also suggeststhat cyclins provide spatial regulation of specific CDK activity,differentially targeting the cytoskeleton, spindle, phragmoplast,nuclear envelope, and chromosomes.

Plant cyclins are classified into five major groups: A, B, C, D, and H.Renaudin et al., Plant Mol. Biol. 32: 1003-18 (1996) and Yamaguchi etal., (supra 2000). Cyclins can be divided into mitotic cyclins (A and B)and G₁ cyclins.

The mitotic cyclins possess a consensus sequence (R-x-x-L-x-x-I-x-N)located at the N-terminal region, termed a destruction box, adjacent toa lysine-rich region. The destruction box and lysine-rich region targetthe mitotic cyclins for ubiquitin-dependent proteolysis during mitosis.Stals, supra at 361, and Fowler, supra at 126. The destruction box in Aversus B cyclins differs slightly and this difference is thought toresult in slightly different timing of degradation of A versus Bcyclins. Fowler, supra at 126. A-type cyclins accumulate during the S,G2, and early M phase of the cell cycle, whereas B-type cyclinsaccumulate during the late G2 and early M phase. Mironov et al., PlantCell 11: 509-22 (1999). Three subgroups of A-type cyclins are known inplants, but only one is known in animals. Cyclin A1 (cycA1;zm;1 from Zeacans) is most concentrated during cytokinesis at themicrotubule-containing phragmoplast. Expression of cyclin A2 isupregulated by auxins in roots, and by cytokinins in the shoot apex.Abrahams et al., Biochim. Biophys. Acta 28: 1-2 (2001).

D-type cyclins, of which five subgroups are known, are thought tocontrol the progression through the G1 phase in response to growthfactors and nutrients. Riou-Khamlichi et al., Mol. Cell Biol. 20:4513-21 (2000). For example, the expression of D-type cyclins isupregulated by sucrose as shown by an increase in cycD2 mRNA 30 minutesafter sucrose exposure, and an increase in cycD3 four hours aftersucrose exposure. This timing corresponds to early G1-phase and lateG1-phase, respectively. Cockcroft et al., Nature 405: 575-9 (2000).Furthermore, in Arabidopsis, a D3 cyclin was shown to be upregulated bythe brassinosteroid, epi-brassinolide.

Cyclin D2 proteins bind with CDKA to produce an active complex, whichbinds to and phosphorylates retinoblastoma-related protein (Rb). Thisprocess is found in actively proliferating tissue, suggesting it playsan important function during late G1- and early S-phase. Three differentD3-type cyclins are active during tomato fruit development. Theseproteins all contain a retinoblastoma binding motif and aPEST-destruction motif. There are differences in the spatial andtemporal expression of these D3 cyclins, inferring different rolesduring fruit development.

Overexpression of cyclin D was shown to increase overall growth rate.Over-expression of cyclin D2 in tobacco increases causes shortening theG1-phase which producing a faster rate of cell cycling.

C- and H-type cyclins were characterized in poplar (Populustremula×tremuloides) and rice (Oryza sativa) but their exact function isstill unclear. Putative cyclins with a lesser degree of peptide sequenceconservation have also been identified. For example, Arabidopsis CycJ18has only 20% identity with homologues over the cyclin box domain. CycJ18is expressed predominantly in young seedlings. Arabidopsis F3O9.13protein also has similarity to the cyclin family.

3. Histone Acetyltransferase/Deacetyltransferase

Histone acetyltransferase (HA) and histone deacetyltransferase (HAD)control the net level of acetylation of histones. Histone acetylationand deacetylation are thought to exert their regulatory effects on geneexpression by altering the accessibility of nucleosomal DNA toDNA-binding transcriptional activators, other chromatin-modifyingenzymes or multi-subunit chromatin remodeling complexes capable ofdisplacing nucleosomes. Lusser et al., Nucleic Acids Res. 27: 4427-35(1999). Therefore, in general, the HDAs are involved in the repressionof gene expression, while HAs are correlated with gene activation.

HA effects acetylation at the ε-amino group of conserved lysine residuesclustered near the amino terminus of core histones which up-regulatesgene expression.

HDAs remove acetyl groups from the core histones of the nucleosome.There are numerous family members in the HDA group, many of which areconserved throughout evolution. Lechner et al., Biochim Biophys Acta5:181-8 (1996). HDAs function as part of multi-protein complexesfacilitating chromatin condensation.

HDAs and HAs recognize highly distinct acetylation patterns on thenucleosome. It is thought that different types of HDAs interact withspecific regions of the genome, to influence gene silencing.

Schultz et al., Genes Dev. 15: 428-43 (2001), demonstrated that thesuperfamily of Kruppel-associated-box zinc finger proteins (KRAB-ZFPs)are linked to the nucleosome remodeling and histone deacetylationcomplex via the PHD (plant homeodomain) and bromodomains of co-repressorKAP-1, to form a cooperative unit that is required for transcriptionalrepression. A maize HDAC (HD2) has been identified that has no sequencehomology to other eukaryotic HDACs, but instead contains sequencesimilarity to peptidyl-prolyl cis-trans isomerases (PPIases).

The effects of interfering with histone deacetylation are discussed ine.g. Tian and Chen, Proc. Nat'l Acad. Sci. USA 98: 200-5 (2001).

4. Peptidyl Prolyl Cis-Trans Isomerase

Peptidylprolyl isomerases (e.g., peptidylprolyl cis-trans isomerase,peptidyl-prolyl cis-trans isomerase, PPIase, rotamase, cyclophilin)catalyze the interconversion of peptide bonds between the cis and transconformations at proline residues. Sheldon and Venis, Biochem J. 315:965-70 (1996). This interconversion is thought to be the rate limitingstep of protein folding. PPIases belong to a conserved family ofproteins that are present in animals, fungi, bacteria and plants.PPIases are implicated in a number of responses including the responseto environmental stress, calcium signals, transcriptional repression,cell cycle control, etc. Viaud, et al., Plant Cell 14: 917-30 (2002).

5. Retinoblastoma-Related Protein

Retinoblastoma (Rb)-related protein putatively regulates progression ofthe cell cycle through the G1 phase and into S phase. Xie et al., EMBOJ. 15: 4900-8 (1996) and Ach et al., Mol. Cell Biol. 17: 5077-86 (1997).

Although Rb is well-characterized in mammalian systems, the role ofRb-related proteins in regulation of G1 phase progression and S phaseentry is not well characterized in plants. It is known, however, thatRB-related protein functions through its association with various othercellular proteins involved in cell cycle regulation, such as thecyclins, WD40 proteins, Soni et al., Plant. Cell. 7:85-103 (1995); Grafiet al., Proc. Natl. Acad. Sci. U.S.A. 93:8962 (1996); Ach et al., PlantCell 9:1595-606 (1997); Umen and Goodenough, Genes Dev. 15:1652-61(2001); Mariconti et al., J. Biol. Chem. 277:9911-9 (2002).

6. WD40 Repeat Protein

WD40 is a common repeating motif involved in many differentprotein-protein interactions. The WD40 domain is found in proteinshaving a wide variety of functions including adaptor/regulatory modulesin signal transduction, pre-mRNA processing and cytoskeleton assembly.Goh et al., Eur. J. Biochem. 267: 434-49 (2000).

The WD40 domain, which is 40 residues long, typically contains a GHdipeptide 11-24 residues from the N-terminus and the WD dipeptide at theC-terminus. Id. Between the GH dipeptide and the WD dipeptide lies aconserved core which serves as a stable platform where proteins can bindeither stably or reversibly. The core forms a propeller-like structurewith several blades. Each blade is composed of a four-strandedanti-parallel β-sheet. Each WD40 sequence repeat forms the first threestrands of one blade and the last strand in the next blade. The lastC-terminal WD40 repeat completes the blade structure of the first WD40repeat to create the closed ring propeller-structure. The residues onthe top and bottom surface of the propeller are proposed to coordinateinteractions with other proteins and/or small ligands.

Studies in yeast demonstrated that Cdc20, which contains the WD40 motif,is required for the proteolysis of mitotic cyclins. This process ismediated by an ubiquitin-protein ligase called anaphase-promotingcomplex (APC) or cyclosome. Following ubiquitination and proteolysis bythe 26S proteasome, the cell can segregate chromosomes, and exit frommitosis. Cdc20 also contains a destruction-box domain.

7. WEE1-Like Protein

WEE1 controls the activity of cyclin-dependent kinases. WEE1 itself is aserine/threonine kinase. Sorrell et al., Planta 215: 518-22 (2002). Theenzymatic activity of these protein kinases is controlled byphosphorylation of specific residues in the activation segment of thecatalytic domain, sometimes combined with reversible conformationalchanges in the C-terminal autoregulatory tail. This process is conservedamong eukaryotes, from fungi to animals and plants. Similarly, there isa high degree of homology between WEE1 proteins from various organisms.For example, there is 50% identity between the protein kinase domains ofthe human and maize WEE1 proteins.

Expression of WEE1 is shown to occur only in actively dividing tissuesand is believed to inhibit cell division by acting as a negativeregulator of mitosis. WEE1 is believed to prevent entry from G2 to M byprotecting the nucleus from cytoplasmically-activated cyclinB1-complexed CDC2 before the onset of mitosis. For example,over-expression of AtWEE1 (from Arabidopsis) and ZmWEE1 (from Zea cans)in fission yeast inhibits cell division which results in elongatedcells. Sun et al., Proc. Nat'l Acad. Sci. USA 96: 4180-5 (1999).

B. Expression Profiling and Microarray Analysis in Plant Development

The multigenic control of plant phenotype presents difficulties indetermining the genes responsible for phenotypic determination. Onemajor obstacle to identifying genes and gene expression differences thatcontribute to phenotype in plants is the difficulty with which theexpression of more than a handful of genes can be studied concurrently.Another difficulty in identifying and understanding gene expression andthe interrelationship of the genes that contribute to plant phenotype isthe high degree of sensitivity to environmental factors that plantsdemonstrate.

There have been recent advances using genome-wide expression profiling.In particular, the use of DNA microarrays has been useful to examine theexpression of a large number of genes in a single experiment. Severalstudies of plant gene responses to developmental and environmentalstimuli have been conducted using expression profiling. For example,microarray analysis was employed to study gene expression during fruitripening in strawberry, Aharoni et al., Plant Physiol. 129:1019-1031(2002), wound response in Arabodopsis, Cheong et al., Plant Physiol.129:661-7 (2002), pathogen response in Arabodopsis, Schenk et al., Proc.Nat'l Acad. Sci. 97:11655-60 (2000), and auxin response in soybean,Thibaud-Nissen et al., Plant Physiol. 132:118. Whetten et al., PlantMol. Biol. 47:275-91 (2001) discloses expression profiling of cell wallbiosynthetic genes in Pinus taeda L. using cDNA probes. Whetten et al.examined genes which were differentially expressed betweendifferentiating juvenile and mature secondary xylem. Additionally, todetermine the effect of certain environmental stimuli on geneexpression, gene expression in compression wood was compared to normalwood. 156 of the 2300 elements examined showed differential expression.Whetten, supra at 285. Comparison of juvenile wood to mature wood showed188 elements as differentially expressed. Id. at 286.

Although expression profiling and, in particular, DNA microarraysprovide a convenient tool for genome-wide expression analysis, their usehas been limited to organisms for which the complete genome sequence ora large cDNA collection is available. See Hertzberg et al., Proc. Nat'lAcad. Sci. 98:14732-7 (2001a), Hertzberg et al., Plant J., 25:585(2001b). For example, Whetten, supra, states, “A more complete analysisof this interesting question awaits the completion of a larger set ofboth pine and poplar ESTs.” Whetten et al. at 286. Furthermore,microarrays comprising cDNA or EST probes may not be able to distinguishgenes of the same family because of sequence similarities among thegenes. That is, cDNAs or ESTs, when used as microarray probes, may bindto more than one gene of the same family.

Methods of manipulating gene expression to yield a plant with a moredesirable phenotype would be facilitated by a better understanding ofcell cycle gene expression in various types of plant tissue, atdifferent stages of plant development, and upon stimulation by differentenvironmental cues. The ability to control plant architecture andagronomically important traits would be improved by a betterunderstanding of how cell cycle gene expression effects formation ofplant tissues, how cell cycle gene expression causes plant cells toenter or exit cell division, and how plant growth and the cell cycle areconnected. Among the large number of genes, the expression of which canchange during development of a plant, only a fraction are likely toeffect phenotypic changes during any given stage of the plantdevelopment.

SUMMARY

Accordingly, there is a need for tools and methods useful in determiningthe changes in the expression of cell cycle genes that occur during theplant cell cycle. There is also a need for polynucleotides useful insuch methods. There is a further need for methods which can correlatechanges in cell cycle gene expression to phenotype or stage of plantdevelopment. There is a further need for methods of identifying cellcycle genes and gene products that impact plant phenotype, and that canbe manipulated to obtain a desired phenotype.

In one aspect, the present invention provides an isolated polynucleotidecomprising a nucleic acid sequence selected from the group consisting ofSEQ ID NOs: 1-237 and conservative variants thereof.

In another aspect, the present invention provides a DNA constructcomprising at least one polynucleotide having the sequence of any one ofSEQ ID NOs: 1-237 and conservative variants thereof.

Another aspect of the invention is a plant cell transformed with a DNAconstruct of comprising a nucleic acid sequence selected from the groupconsisting of SEQ ID NOs: 1-237 and conservative variants thereof.

A further aspect of the invention is a transgenic plant comprising aplant cell transformed with a DNA construct comprising a nucleic acidsequence selected from the group consisting of SEQ ID NOs: 1-237 andconservative variants thereof.

Another aspect of the invention is an isolated polynucleotide comprisinga sequence encoding the catalytic or substrate-binding domain of apolypeptide selected from of any one of SEQ ID NOs: 261-497, wherein thepolynucleotide encodes a polypeptide having the activity of saidpolypeptide selected from any one of SEQ ID NOs: 261-497.

A further aspect of the invention is a method of making a transformedplant comprising transforming a plant cell with a DNA constructcomprising at least one polynucleotide having the sequence of any of SEQID NOs: 1-237; and culturing the transformed plant cell under conditionsthat promote growth of a plant.

In another aspect, the invention provides a wood obtained from atransgenic tree.

In a further aspect, the invention provides a wood pulp obtained from atransgenic tree which has been transformed with the DNA construct of theinvention.

Another aspect of the invention is a method of making wood, comprisingtransforming a plant with a DNA construct comprising a polynucleotidehaving a nucleic acid sequence selected from the group consisting of SEQID NOs: 1-237 and conservative variants thereof; culturing thetransformed plant under conditions that promote growth of a plant; andobtaining wood from the plant.

The invention further provides a method of making wood pulp, comprisingtransforming a plant with a DNA construct comprising a polynucleotidehaving a nucleic acid sequence selected from the group consisting of SEQID NOs: 1-237 and conservative variants thereof; culturing thetransformed plant under conditions that promote growth of a plant; andobtaining wood pulp from the plant.

In another aspect, the invention provides an isolated polypeptidecomprising an amino acid sequence encoded by the isolated polynucleotidecomprising a nucleic acid sequence selected from the group consisting ofSEQ ID NOs: 1-237 and conservative variants thereof.

The invention also provides, an isolated polypeptide comprising an aminoacid sequence selected from the group consisting of 261-497.

The invention further provides a method of altering a plant phenotype ofa plant, comprising altering expression in the plant of a polypeptideencoded by any one of SEQ ID NOs: 1-237.

In another aspect, the invention provides a polynucleotide comprising anucleic acid selected from the group comprising of SEQ ID NOs: 471-697.

An aspect of the invention is a method of correlating gene expression intwo different samples, comprising detecting a level of expression of oneor more genes encoding a product encoded by a nucleic acid sequenceselected from the group consisting of SEQ ID NOs: 1-237 and conservativevariants thereof in a first sample; detecting a level of expression ofthe one or more genes in a second sample; comparing the level ofexpression of the one or more genes in the first sample to the level ofexpression of the one or more genes in the second sample; andcorrelating a difference in expression level of the one or more genesbetween the first and second samples.

A further aspect of the invention is a method of correlating thepossession of a plant phenotype to the level of gene expression in theplant of one or more genes comprising detecting a level of expression ofone or more genes encoding a product encoded by a nucleic acid sequenceselected from the group consisting of SEQ ID NOs: 1-237 and conservativevariants thereof in a first plant possessing a phenotype; detecting alevel of expression of the one or more genes in a second plant lackingthe phenotype; comparing the level of expression of the one or moregenes in the first plant to the level of expression of the one or moregenes in the second plant; and correlating a difference in expressionlevel of the one or more genes between the first and second plants topossession of the phenotype.

In a further aspect, the invention provides a method of correlating geneexpression to a stage of the cell cycle, comprising detecting a level ofexpression of one or more genes encoding a product encoded by a nucleicacid sequence selected from the group consisting of SEQ ID NOs: 1-237and conservative variants thereof in a first plant cell in a first stageof the cell cycle; detecting a level of expression of the one or moregenes in a second plant cell in a second, different stage of the cellcycle; comparing the level of the expression of the one or more genes inthe first plant cells to the level of expression of the one or moregenes in the second plants cells; and correlating a difference inexpression level of the one or more genes between the first and secondsamples to the first or second stage of the cell cycle.

An aspect of the invention is a combination for detecting expression ofone or more genes, comprising two or more oligonucleotides, wherein eacholigonucleotide is capable of hybridizing to a nucleic acid sequenceselected from the group consisting of SEQ ID NOs: 1-237.

Another aspect of the invention is a combination for detectingexpression of one or more genes, comprising two or moreoligonucleotides, wherein each oligonucleotide is capable of hybridizingto a nucleic acid sequence encoded by a nucleic acid sequence selectedfrom the group consisting of SEQ ID NOs: 1-237.

The invention further provides a microarray comprising a combination fordetecting expression of one or more genes, comprising two or moreoligonucleotides, wherein each oligonucleotide is capable of hybridizingto a nucleic acid sequence selected from the group consisting of SEQ IDNOs: 1-237 or wherein each oligonucleotide is capable of hybridizing toa nucleic acid sequence encoded by a nucleic acid sequence selected fromthe group consisting of SEQ ID NOs: 1-237, wherein each of said two ormore oligonucleotides occupies a unique location on said solid support.

In another aspect, the invention provides a method for detecting one ormore genes in a sample, comprising contacting the sample with two ormore oligonucleotides, wherein each oligonucleotide is capable ofhybridizing to a gene comprising a nucleic acid sequence selected fromthe group consisting of SEQ ID NOs: 1-237 under standard hybridizationconditions; and detecting the one or more genes of interest which arehybridized to the one or more oligonucleotides.

The invention also provides a method for detecting one or more nucleicacid sequences encoded by one or more genes in a sample, comprisingcontacting the sample with two or more oligonucleotides, wherein eacholigonucleotide is capable of hybridizing to a nucleic acid sequenceencoded by a gene comprising a nucleic acid sequence selected from thegroup consisting of SEQ ID NOs: 1-237 under standard hybridizationconditions; and detecting the one or more nucleic acid sequences whichare hybridized to the one or more oligonucleotides.

The invention further provides a kit for detecting gene expressioncomprising the microarray of the invention together with one or morebuffers or reagents for a nucleotide hybridization reaction.

Other features, objects, and advantages of the present invention areapparent from the detailed description that follows. It should beunderstood, however, that the detailed description, while indicatingpreferred embodiments of the invention, are given by way of illustrationonly, not limitation. Various changes and modifications within thespirit and scope of the invention will be apparent to those skilled inthe art from the detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Exemplary microarray sampling parameters.

FIG. 2: Plasmid map for pWVK202.

FIG. 3: Plasmid map for pGrowth14.

FIG. 4: Plasmid map for pGrowth15.

FIG. 5: Plasmid map for pGrowth16.

FIG. 6: Plasmid map for pGrowth18.

FIG. 7: Plasmid map for pGrowth19.

FIG. 8: Plasmid map for pGrowth20.

LIST OF TABLES

Table 1: shows genes having greater than doubled signal with any onesample as compared to the mean signal of the other three samples.

Table 2: identifies plasmid(s), genes, and Genesis ID numbers forconstructs described in Example 17.

Table 3: Rooting medium for Populus deltoids.

Table 4: pGrowth information.

Table 5: shows genes having greater than doubled signal with any onesample as compared to the mean signal of the other three samples.

Table 6: Differentially expressed cDNAs.

Table 7: Consensus ID information.

Table 8: pGrowth information.

Table 9: Eucalyptus grandis cell cycle genes and proteins.

Table 10: Pinus radiata cell cycle genes and proteins.

Table 11: Annotated peptide sequences of the present invention.

Table 12: Eucalyptus in silico data.

Table 13: Pine in silico data.

Table 14: Oligo table.

Table 15: Peptide table.

Table 16: BLAST sequence alignment table.

DETAILED DESCRIPTION

The inventors have discovered novel isolated cell cycle genes andpolynucleotides useful for identifying the multigenic factors thatcontribute to a phenotype and for manipulating gene expression to affecta plant phenotype. These genes, which are derived from plants ofcommercially important forestry genera, pine and eucalyptus, areinvolved in the plant cell cycle and are, at least in part, responsiblefor expression of phenotypic characteristics important in commercialwood, such as stiffness, strength, density, fiber dimensions,coarseness, cellulose and lignin content, and extractives content.Generally speaking, the genes and polynucleotides encode a protein whichcan be a cyclin, cyclin dependent kinase, cyclin dependent kinaseinhibitor, histone acetyltransferase, histone deacetylase,peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein,WEE1-like protein, or WD40 repeat protein, or a catalytic domainthereof, or a polypeptide having the same function, and the inventionfurther includes such proteins and polypeptides.

The methods of the present invention for selecting cell cycle genesequences to target for manipulation will permit better design andcontrol of transgenic plants with more highly engineered phenotypes. Theability to control plant architecture and agronomically important traitsin commercially important forestry species will be improved by theinformation obtained from the methods, such as which genes affect whichphenotypes, which genes affect entry into which stage of the cell cycle,which genes are active in which stage of plant development, and whichgenes are expressed in which tissue at a given point in the cell cycleor plant development.

Unless indicated otherwise, all technical and scientific terms are usedherein in a manner that conforms to common technical usage. Generally,the nomenclature of this description and the described laboratoryprocedures, including cell culture, molecular genetics, and nucleic acidchemistry and hybridization, respectively, are well known and commonlyemployed in the art. Standard techniques are used for recombinantnucleic acid methods, oligonucleotide synthesis, cell culture, tissueculture, transformation, transfection, transduction, analyticalchemistry, organic synthetic chemistry, chemical syntheses, chemicalanalysis, and pharmaceutical formulation and delivery. Generally,enzymatic reactions and purification and/or isolation steps areperformed according to the manufacturers' specifications. Absent anindication to the contrary, the techniques and procedures in questionare performed according to conventional methodology disclosed, forexample, in Sambrook et al., MOLECULAR CLONING A LABORATORY MANUAL, 2ded. (Cold Spring Harbor Laboratory Press, 1989), and CURRENT PROTOCOLSIN MOLECULAR BIOLOGY, John Wiley & Sons, 1989). Specific scientificmethods relevant to the present invention are discussed in more detailbelow. However, this discussion is provided as an example only, and doesnot limit the manner in which the methods of the invention can becarried out.

A. Plant Cell Cycle Genes and Proteins

1. Cell Cycle Genes, Polynucleotide and Polypeptide Sequences

One aspect of the present invention relates to novel plant cell cyclegenes and polypeptides encoded by such genes. As used herein, the term“plant cell cycle genes” refers to genes encoding proteins that functionduring the plant cell cycle, and the term “plant cell cycle proteins”refers to proteins that function during the plant cell cycle. There areseveral known families of plant cell cycle proteins, including cyclin,cyclin dependent kinase, cyclin dependent kinase inhibitor, histoneacetyltransferase, histone deacetylase, peptidyl-prolyl cis-transisomerase, retinoblastoma-related protein, WEE1-like protein, and WD40repeat protein. Although there is significant sequence homology withineach gene and protein family, each member of each family can displaydifferent biochemical properties and altering the expression of at leastone of these genes can result in a different plant phenotype.

The present invention provides novel plant cell cycle genes andpolynucleotides and novel cell cycle proteins and polypeptides. Inaccordance with one embodiment of the invention, the novel plant cellcycle genes are the same as those expressed in a wild-type plant of aspecies of Pinus or Eucalyptus. Exemplary novel plant cell cycle genesequences of the invention are set forth in Tables 9 and 10, whichdepict Eucalyptus grandis sequences and Pinus radiata sequences,respectively. Corresponding gene products, i.e., oligonucleotides andpolypeptides, are also listed in Tables 14, 15, and 16. The SequenceListing in APPENDIX 1 provides the sequences of these aspects of theinvention.

The sequences of the invention have cell cycle activity and encodeproteins that are active in the cell cycle, such as proteins of the cellcycle families discussed above. As discussed in more detail below,manipulation of the expression of the cell cycle genes andpolynucleotides, or manipulation of the activity of the encoded proteinsand polypeptides, can result in a transgenic plant with a desiredphenotype that differs from the phenotype of a wild-type plant of thesame species.

Throughout this description, reference is made to cell cycle geneproducts. As used herein, a “cell cycle gene product” is a productencoded by a cell cycle gene, and includes both nucleotide products,such as RNA, and amino acid products, such as proteins and polypeptides.Examples of specific cell cycle genes of the invention include SEQ IDNOs: 1-237. Examples of specific cell cycle gene products of theinvention include products encoded by any one of SEQ ID NOs: 1-237.Reference also is made herein to cell cycle proteins and cell cyclepolypeptides. Examples of specific cell cycle proteins and polypeptidesof the invention include polypeptides encoded by any of SEQ ID NOs:1-237 or polypeptides comprising the amino acid sequence of any of SEQID NOs: 261-497. One aspect of the invention is directed to a subset ofthese cell cycle genes and cell cycle gene products, namely SEQ ID NOs:1-12, 14-58, 60-62, 64-70, 72-75, 77-83, 85-86, 88-91, 93-119, 121-130,132-148, 150-156, 158-191, 193-207, 209-218, 220-221, 223-231, 233-237,their respective conservative variants (as that term is defined below),and the nucleotide and amino acid products encoded thereby. Anotheraspect of the invention is directed to a subset of the cell cycle genesand cell cycle gene products, namely SEQ ID NOs: 1-12, 14, 16-26, 30-37,40-41, 43-76, 78-103, 106, 108-113, 116-121, 124-125, 128-147, 150-152,154-155, 161-162, 164-172, 174, 177-183, 185-191, 193-197, 200-204,208-213, and 215-234 their respective conservative variants, and thenucleotide and amino acid products encoded thereby. A further aspect ofthe invention is directed to a subset of the cell cycle genes and cellcycle gene products, namely SEQ ID NOs: 1-12, 14, 16-26, 30-37, 40-41,43-58, 60-62, 64-70, 72-75, 78-83, 85-86, 88-91, 93-103, 106, 108-113,116-119, 121, 124-125, 128-130, 132-147, 150-152, 154-155, 161-162,164-172, 174, 177-183, 185-191, 193-197, 200-204, 209-213, 215-218,220-221, 223-231, and 233-234 their respective conservative variants,and the nucleotide and amino acid products encoded thereby.

The present invention also includes sequences that are complements,reverse sequences, or reverse complements to the nucleotide sequencesdisclosed herein.

The present invention also includes conservative variants of thesequences disclosed herein. The term “variant,” as used herein, refersto a nucleotide or amino acid sequence that differs in one or morenucleotide bases or amino acid residues from the reference sequence ofwhich it is a variant.

Thus, in one aspect, the invention includes conservative variantpolynucleotides. As used herein, the term “conservative variantpolynucleotide” refers to a polynucleotide that hybridizes understringent conditions to an oligonucleotide probe that, under comparableconditions, binds to the reference gene the conservative variant is avariant of. Thus, for example, a conservative variant of SEQ ID NO: 1hybridizes under stringent conditions to an oligonucleotide probe that,under comparable conditions, binds to SEQ ID NO: 1. One aspect of theinvention provides conservative variant polynucleotides that exhibit atleast about 75% sequence identity to their respective referencesequences.

“Sequence identity” has an art-recognized meaning and can be calculatedusing published techniques. See COMPUTATIONAL MOLECULAR BIOLOGY, Lesk,ed. (Oxford University Press, 1988), BIOCOMPUTING: INFORMATICS ANDGENOME PROJECTS, Smith, ed. (Academic Press, 1993), COMPUTER ANALYSIS OFSEQUENCE DATA, PART I, Griffin & Griffin, eds., (Humana Press, 1994),SEQUENCE ANALYSIS IN MOLECULAR BIOLOGY, Von Heinje ed., Academic Press(1987), SEQUENCE ANALYSIS PRIMER, Gribskov & Devereux, eds. (MacmillanStockton Press, 1991), and Carillo & Lipton, SIAM J. Applied Math. 48:1073 (1988). Methods commonly employed to determine identity orsimilarity between two sequences include but are not limited to thosedisclosed in GUIDE TO HUGE COMPUTERS, Bishop, ed., (Academic Press,1994) and Carillo & Lipton, supra. Methods to determine identity andsimilarity are codified in computer programs. Preferred computer programmethods to determine identity and similarity between two sequencesinclude but are not limited to the GCG program package (Devereux et al.,Nucleic Acids Research 12: 387 (1984)), BLASTP, BLASTN, FASTA (Atschulet al., J. Mol. Biol. 215: 403 (1990)), and FASTDB (Brutlag et al.,Comp. App. Biosci. 6: 237 (1990)).

The invention includes conservative variant polynucleotides having asequence identity that is greater than or equal to 99%, 98%, 97%, 96%,95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%,81%, 80%, 79%, 78%, 77%, 76%, 75%, 74%, 73%, 72%, 71%, 70%, 69%, 68%,67%, 66%, 65%, 64%, 63%, 62%, 61%, or 60% to any one of SEQ ID NOs: 1 to237. In such variants, differences between the variant and the referencesequence can occur at the 5′ or 3′ terminal positions of the referencenucleotide sequence or anywhere between those terminal positions,interspersed either individually among nucleotides in the referencesequence or in one or more contiguous groups within the referencesequence.

Additional conservative variant polynucleotides contemplated by andencompassed within the present invention include polynucleotidescomprising sequences that differ from the polynucleotide sequences ofSEQ ID NO: 1-237, or complements, reverse complements or reversesequences thereof, as a result of deletions and/or insertions totalingless than 10% of the total sequence length.

The invention also includes conservative variant polynucleotides that,in addition to sharing a high degree of similarity in their primarystructure (sequence) to SEQ ID NOs: 1 to 237, have at least one of thefollowing features: (i) they contain an open reading frame or partialopen reading frame encoding a polypeptide having substantially the samefunctional properties in the cell cycle as the polypeptide encoded bythe reference polynucleotide, or (ii) they have nucleotide domains orencoded protein domains in common. The invention includes conservativevariants of SEQ ID NOs: 1-237 that encode proteins having the enzyme orbiological activity or binding properties of the protein encoded by thereference polynucleotide. Such conservative variants are functionalvariants, in that they have the enzymatic or binding activity of theprotein encoded by the reference polynucleotide.

In accordance with the invention, polynucleotide variants can include a“shuffled gene” such as those described in e.g. U.S. Pat. Nos.6,500,639, 6,500,617 6,436,675, 6,379,964, 6,352,859 6,335,1986,326,204, and 6,287,862. A variant of a nucleotide sequence of thepresent invention also can be a polynucleotide modified as disclosed inU.S. Pat. No. 6,132,970, which is incorporated herein by reference.

In accordance with one embodiment, the invention provides apolynucleotide that encodes a cell cycle protein from one of thefollowing families: cyclin, cyclin dependent kinase, cyclin dependentkinase inhibitor, histone acetyltransferase, histone deacetylase,peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein,WEE1-like protein, or WD40 repeat protein. SEQ ID NOs: 1-237 provideexamples of such polynucleotides.

In accordance with another embodiment, a polynucelotide of the inventionencodes the catalytic or protein binding domain of a polypeptide encodedby any of SEQ ID NOs: 1-237 or of a polypeptide comprising any of SEQ IDNOs: 261-497. The catalytic and protein binding domains of the cellcycle proteins of the invention are known in the art. The conservedsequences of these proteins are shown in Entries 1-195 as underlined,bold, and/or italicized text.

The invention also encompasses as conservative variants polynucleotidesthat differ from the sequences discussed above but that, as aconsequence of the degeneracy of the genetic code, encode a polypeptidewhich is the same as that encoded by a polynucleotide of the presentinvention. The invention also includes as conservative variantspolynucleotides comprising sequences that differ from the polynucleotidesequences discussed above as a result of substitutions that do notaffect the amino acid sequence of the encoded polypeptide sequence, orthat result in conservative substitutions in the encoded polypeptidesequence.

The present invention also includes an isolated polypeptide encoded by apolynucleotide comprising any of SEQ ID NOs: 1-237 or any of theconservative variants thereof discussed above. The invention alsoincludes polypeptides comprising SEQ ID NOs: 261-497 and 495-497 andconservative variants of these polypeptides. Another aspect of theinvention include polypeptides comprising SEQ ID NOs: 261-272, 274-318,320-322, 324-330, 332-335, 337-343, 345-346, 348-351, 353-379, 381-390,392-408, 410-416, 418-451, 453-467, 469-478, 480-481, 483-491, and493-494 and conservative variants thereof. A further aspect of theinvention includes polypeptides comprising SEQ ID NOs: 261-272, 274,276-286, 289, 290-297, 300-301, 303-345, 347-363, 366, 368-373, 376-381,384-385, 388-407, 410-412, 414-415, 420-422, 424-432, 434, 437-443,445-451, 453-457, 460-464, 468-473, and 475-494 and conservativevariants thereof. Another aspect of the invention includes polypeptidescomprising SEQ ID NOs: 261-272, 274, 276-286, 290-297, 300-301, 303-318,320-322, 324-330, 332-335, 337-343, 345, 348-351, 353-363, 366, 368-373,376-381, 384-385, 388-390, 392-407, 410-412, 414-415, 421-422, 424-432,434, 437-443, 445-451, 453-457, 460-464, 469-473, 475-478, 480-481,483-491, and 493-494 and conservative variants thereof.

In accordance with the invention, a variant polypeptide or proteinrefers to an amino acid sequence that is altered by the addition,deletion or substitution of one or more amino acids.

The invention includes conservative variant polypeptides. As usedherein, the term “conservative variant polypeptide” refers to apolypeptide that has similar structural, chemical or biologicalproperties to the protein it is a conservative variant of. Guidance indetermining which amino acid residues can be substituted, inserted, ordeleted can be found using computer programs well known in the art suchas Vector NTI Suite (InforMax, MD) software. In one embodiment of theinvention, conservative variant polypeptides that exhibit at least about75% sequence identity to their respective reference sequences.

Conservative variant protein includes an “isoform” or “analog” of thepolypeptide. Polypeptide isoforms and analogs refers to proteins havingthe same physical and physiological properties and the same biologicalfunction, but whose amino acid sequences differs by one or more aminoacids or whose sequence includes a non-natural amino acid.

Polypeptides comprising sequences that differ from the polypeptidesequences of SEQ ID NO: 261-497 as a result of amino acid substitutions,insertions, and/or deletions totaling less than 10% of the totalsequence length are contemplated by and encompassed within the presentinvention.

One aspect of the invention provides conservative variant polypeptidesthat have the same function in the cell cycle as the proteins of whichthey are variants, as determined by one or more appropriate assays, suchas those described below. The invention includes variant polypeptidesthat function as cell cycle proteins, such as those having thebiological activity of cyclin, cyclin dependent kinase, cyclin dependentkinase inhibitor, histone acetyltransferase, histone deacetylase,peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein,WEE1-like protein, and WD40 repeat protein, and are thus capable ofmodulating the cell cycle in a plant. As discussed above, the inventionincludes variant polynucleotides that encode polypeptides that functionas cell cycle proteins.

The activities and physical properties of cell cycle proteins can beexamined using any method known in the art. The following examples ofassay methods are not exhaustive and are included to provide someguidance in examining the activity and distinguishing proteincharacteristics of cell cycle protein variants.

CDK activity can be assessed using roscovitine as described in Yamaguchiet al., Proc. Natl. Acad. Sci. U.S.A. 100:8019 (2003). CDK histonekinase activity can be assayed using autoradiography to detect histoneH1 phosphorylation by CDK as described in Joubés et al., Plant Physiol.121:857 (1999).

CKI activity can be assayed using a variation of the method described inZhou et al., Planta. 6:604 (2003). The modified method can employco-transformation or subsequent transformations to identify theinteraction of CKI and cyclins in vivo. For example, in the firsttransformation pine tissue can be transformed using the method describedin U.S. Patent Application Publication No. 2002/0100083 using geneticinselection to obtain transgenic plants possessing cycD3 and cdc2ahomologs. The second transformation can be performed usingalpha-methyltryptophan as a selectable marker to obtain transformantshaving an ICK1 homologue as described in U.S. Provisional ApplicationNo. 60/476,189. Tissue capable of growing on both on geneticin and onalpha-methyltryptophan contains the ICK1 homologue and the cycD3 andcdc2a homologues. The CKI activity is determined by comparison of thephenotype of transformants having the cycD3 and cdc2a homologues to thetransformants having ICK1 homologue and the cycD3 and cdc2a homologs.

Histone deacetylase activity can be assessed by complementation of theArabidopsis mutants described in Tian et al., Genetics 165:399 (2003).Histone acetyltransferase activity can be assayed using anacardic acidas described in Balasubramanyam et al., J. Biol. Chem. 278:19134 (2003).Histone acetyltransferase also can be assayed using trichostatinA-treated plant lines as is described in Bhat et al., Plant J. 33:455(2003). The plant lines described in Bhat et al., supra, also can beused to assay retinoblastoma-related proteins using the co-precipitationmethod described in Rossi et al., Plant Mol. Biol. 51:401 (2003).

Peptidyl-prolyl isomerase can be assayed as described in Edvardsson etal., FEBS Lett. 542:137 (2003). WD40 proteins can be evaluated based onthe possession of the WD40 motif as well as their ability to interactwith cdc2. WEE-1 can be assayed using any kinase activity assay known inthe art.

2. Methods of Using Cell Cycle Genes, Polynucleotide and PolypeptideSequences

The present invention provides methods of using plant cell cycle genesand conservative variants thereof. The invention includes methods andconstructs for altering expression of plant cell cycle genes and/or geneproducts for purposes including, but not limited to (i) investigatingfunction during the cell cycle and ultimate effect on plant phenotypeand (ii) to effect a change in plant phenotype. For example, theinvention includes methods and tools for modifying wood quality, fiberdevelopment, cell wall polysaccharide content, fruit ripening, and plantgrowth and yield by altering expression of one or more plant cell cyclegenes.

The invention comprises methods of altering the expression of any of thecell cycle genes and variants discussed above. Thus, for example, theinvention comprises altering expression of a cell cycle gene present inthe genome of a wild-type plant of a species of Eucalyptus or Pinus. Inone embodiment, the cell cycle gene comprises a nucleotide sequenceselected from SEQ ID NOs: 1-237, from the subset thereof comprising SEQID NOs: SEQ ID NOs: 1-12, 14-58, 60-62, 64-70, 72-75, 77-83, 85-86,88-91, 93-119, 121-130, 132-148, 150-156, 158-191, 193-207, 209-218,220-221, 223-231, and 233-237, from the subset thereof comprising SEQ IDNOs: 1-12, 14, 16-26, 30-37, 40-41, 43-76, 78-103, 106, 108-113,116-121, 124-125, 128-147, 150-152, 154-155, 161-162, 164-172, 174,177-183, 185-191, 193-197, 200-204, 208-213, and 215-234, from thesubset thereof comprising SEQ ID NOs: 1-12, 14, 16-26, 30-37, 40-41,43-58, 60-62, 64-70, 72-75, 78-83, 85-86, 88-91, 93-103, 106, 108-113,116-119, 121, 124-125, 128-130, 132-147, 150-152, 154-155, 161-162,164-172, 174, 177-183, 185-191, 193-197, 200-204, 209-213, 215-218,220-221, 223-231, and 233-234, or the conservative variants thereof, asdiscussed above.

Techniques which can be employed in accordance with the presentinvention to alter gene expression, include, but are not limited to: (i)over-expressing a gene product, (ii) disrupting a gene's transcript,such as disrupting a gene's mRNA transcript; (iii) disrupting thefunction of a polypeptide encoded by a gene, or (iv) disrupting the geneitself Over-expression of a gene product, the use of antisense RNAs,ribozymes, and the use of double-stranded RNA interference (dsRNAi) arevaluable techniques for discovering the functional effects of a gene andfor generating plants with a phenotype that is different from awild-type plant of the same species.

Over-expression of a target gene often is accomplished by cloning thegene or cDNA into an expression vector and introducing the vector intorecipient cells. Alternatively, over-expression can be accomplished byintroducing exogenous promoters into cells to drive expression of genesresiding in the genome. The effect of over-expression of a given gene oncell function, biochemical and/or physiological properties can then beevaluated by comparing plants transformed to over-express the gene toplants that have not been transformed to over-express the gene.

Antisense RNA, ribozyme, and dsRNAi technologies typically target RNAtranscripts of genes, usually mRNA. Antisense RNA technology involvesexpressing in, or introducing into, a cell an RNA molecule (or RNAderivative) that is complementary to, or antisense to, sequences foundin a particular mRNA in a cell. By associating with the mRNA, theantisense RNA can inhibit translation of the encoded gene product. Theuse of antisense technology to reduce or inhibit the expression ofspecific plant genes has been described, for example in European PatentPublication No. 271988, Smith et al., Nature, 334:724-726 (1988); Smithet. al., Plant Mol. Biol., 14:369-379 (1990)).

A ribozyme is an RNA that has both a catalytic domain and a sequencethat is complementary to a particular mRNA. The ribozyme functions byassociating with the mRNA (through the complementary domain of theribozyme) and then cleaving (degrading) the message using the catalyticdomain.

RNA interference (RNAi) involves a post-transcriptional gene silencing(PTGS) regulatory process, in which the steady-state level of a specificmRNA is reduced by sequence-specific degradation of the transcribed,usually fully processed mRNA without an alteration in the rate of denovo transcription of the target gene itself. The RNAi technique isdiscussed, for example, in Elibashir, et al., Methods Enzymol. 26: 199(2002); McManus & Sharp, Nature Rev. Genetics 3: 737 (2002); PCTapplication WO 01/75164; Martinez et al., Cell 110: 563 (2002); Elbashiret al., supra; Lagos-Quintana et al., Curr. Biol. 12: 735 (2002); Tuschlet al., Nat. Biotechnol. 20:446 (2002); Tuschl, Chembiochem. 2: 239(2001); Harborth et al., J. Cell Sci. 114: 4557 (2001); et al., EMBO J.20:6877 (2001); Lagos-Quintana et al., Science. 294: 8538 (2001);Hutvagner et al., loc cit, 834; Elbashir et al., Nature. 411: 494(2001).

The present invention provides a DNA construct comprising at least onepolynucleotide of SEQ ID NOs: 1-235 or conservative variants thereof,such as the conservative variants discussed above. Any method known inthe art can be used to generate the DNA constructs of the presentinvention. See, e.g. Sambrook et al., supra.

The invention includes DNA constructs that optionally comprise apromoter. Any suitable promoter known in the art can be used. A promoteris a nucleic acid, preferably DNA, that binds RNA polymerase and/orother transcription regulatory elements. As with any promoter, thepromoters of the invention facilitate or control the transcription ofDNA or RNA to generate an mRNA molecule from a nucleic acid moleculethat is operably linked to the promoter. The RNA can encode a protein orpolypeptide or can encode an antisense RNA molecule or a molecule usefulin RNAi. Promoters useful in the invention include constitutivepromoters, inducible promoters, temporally regulated promoters andtissue-preferred promoters.

Examples of useful constitutive plant promoters include: the cauliflowermosaic virus (CaMV) 35S promoter, which confers constitutive, high-levelexpression in most plant tissues (Odel et al. Nature 313:810(1985)); thenopaline synthase promoter (An et al. Plant Physiol. 88:547 (1988)); andthe octopine synthase promoter (Fromm et al., Plant Cell 1: 977 (1989)).It should be noted that, although the CaMV 35S promoter is commonlyreferred to as a constitutive promoter, some tissue preference can beseen. The use of CaMV 35S is envisioned by the present invention,regardless of any tissue preference which may be exhibited during use inthe present invention.

Inducible promoters regulate gene expression in response toenvironmental, hormonal, or chemical signals. Examples of hormoneinducible promoters include auxin-inducible promoters (Baumann et al.Plant Cell 11:323-334(1999)), cytokinin-inducible promoters(Guevara-Garcia, Plant Mol. Biol. 38:743-753(1998)), andgibberellin-responsive promoters (Shi et al. Plant Mol. Biol.38:1053-1060(1998)). Additionally, promoters responsive to heat, light,wounding, pathogen resistance, and chemicals such as methyl jasmonate orsalicylic acid, can be used in the DNA constructs and methods of thepresent invention.

Tissue-preferred promoters allow for preferred expression ofpolynucleotides of the invention in certain plant tissue.Tissue-preferred promoters are also useful for directing the expressionof antisense RNA or siRNA in certain plant tissues, which can be usefulfor inhibiting or completely blocking the expression of targeted genesas discussed above. As used herein, vascular plant tissue refers toxylem, phloem or vascular cambium tissue. Other preferred tissueincludes apical meristem, root, seed, and flower. In one aspect, thetissue-preferred promoters of the invention are either“xylem-preferred,” “cambium-preferred” or “phloem-preferred,” andpreferentially direct expression of an operably linked nucleic acidsequence in the xylem, cambium or phloem, respectively. In anotheraspect, the DNA constructs of the invention comprise promoters that aretissue-specific for xylem, cambium or phloem, wherein the promoters areonly active in the xylem, cambium or phloem.

A vascular-preferred promoter is preferentially active in any of thexylem, phloem or cambium tissues, or in at least two of the three tissuetypes. A vascular-specific promoter is specifically active in any of thexylem, phloem or cambium, or in at least two of the three. In otherwords, the promoters are only active in the xylem, cambium or phloemtissue of plants. Note, however, that because of solute transport inplants, a product that is specifically or preferentially expressed in atissue may be found elsewhere in the plant after expression hasoccurred.

In another embodiment, the promoter is under temporal regulation,wherein the ability of the promoter to initiate expression is linked tofactors such as the stage of the cell cycle or the stage of plantdevelopment. For example, the promoter of a cyclin D2 gene may beexpressed only during the G1 and early S-phase, and the promoters ofparticular cyclin genes may be expressed only within the primaryvascular poles of the developing seedling.

Additionally, the promoters of particular cell cycle genes may beexpressed only within the cambium in developing secondary vasculature.Within the cambium, particular cell cycle gene promoters may beexpressed exclusively in the stem or in the root. Moreover, the cellcycle promoters may be expressed only in the spring (for early woodformation) or only in the summer.

A promoter may be operably linked to the polynucleotide. As used in thiscontext, operably linked refers to linking a polynucleotide encoding astructural gene to a promoter such that the promoter controlstranscription of the structural gene. If the desired polynucleotidecomprises a sequence encoding a protein product, the coding region canbe operably linked to regulatory elements, such as to a promoter and aterminator, that bring about expression of an associated messenger RNAtranscript and/or a protein product encoded by the desiredpolynucleotide. In this instance, the polynucleotide is operably linkedin the 5′- to 3′-orientation to a promoter and, optionally, a terminatorsequence.

Alternatively, the invention provides DNA constructs comprising apolynucleotide in an “antisense” orientation, the transcription of whichproduces nucleic acids that can form secondary structures that affectexpression of an endogenous cell cycle gene in the plant cell. Inanother variation, the DNA construct may comprise a polynucleotide thatyields a double-stranded RNA product upon transcription that initiatesRNA interference of a cell cycle gene with which the polynucleotide isassociated. A polynucleotide of the present invention can be positionedwithin a t-DNA, such that the left and right t-DNA border sequencesflank or are on either side of the polynucleotide.

It should be understood that the invention includes DNA constructscomprising one or more of any of the polynucleotides discussed above.Thus, for example, a construct may comprise a t-DNA comprising one, two,three, four, five, six, seven, eight, nine, ten, or morepolynucleotides.

The invention also includes DNA constructs comprising a promoter thatincludes one or more regulatory elements. Alternatively, the inventionincludes DNA constructs comprising a regulatory element that is separatefrom a promoter. Regulatory elements confer a number of importantcharacteristics upon a promoter region. Some elements bind transcriptionfactors that enhance the rate of transcription of the operably linkednucleic acid. Other elements bind repressors that inhibit transcriptionactivity. The effect of transcription factors on promoter activity candetermine whether the promoter activity is high or low, i.e. whether thepromoter is “strong” or “weak.”

A DNA construct of the invention can include a nucleotide sequence thatserves as a selectable marker useful in identifying and selectingtransformed plant cells or plants. Examples of such markers include, butare not limited to, a neomycin phosphotransferase (nptII) gene (Potrykuset al., Mol. Gen. Genet. 199:183-188 (1985)), which confers kanamycinresistance. Cells expressing the nptII gene can be selected using anappropriate antibiotic such as kanamycin or G418. Other commonly usedselectable markers include a mutant EPSP synthase gene (Hinchee et al.,Bio/Technology 6:915-922 (1988)), which confers glyphosate resistance;and a mutant acetolactate synthase gene (ALS), which confersimidazolinone or sulphonylurea resistance (European Patent Application154,204, 1985).

The present invention also includes vectors comprising the DNAconstructs discussed above. The vectors can include an origin ofreplication (replicons) for a particular host cell. Various prokaryoticreplicons are known to those skilled in the art, and function to directautonomous replication and maintenance of a recombinant molecule in aprokaryotic host cell.

In one embodiment, the present invention utilizes a pWVR8 vector asdescribed in U.S. Application No. 60/476,222, filed Jun. 6, 2003, orpART27 as described in Gleave, Plant Mol. Biol, 20:1203-27 (1992).

The invention also provides host cells which are transformed with theDNA constructs of the invention. As used herein, a host cell refers tothe cell in which a polynucleotide of the invention is expressed.Accordingly, a host cell can be an individual cell, a cell culture orcells that are part of an organism. The host cell can also be a portionof an embryo, endosperm, sperm or egg cell, or a fertilized egg. In oneembodiment, the host cell is a plant cell.

The present invention further provides transgenic plants comprising theDNA constructs of the invention. The invention includes transgenicplants that are angiosperms or gymnosperms. The DNA constructs of thepresent invention can be used to transform a variety of plants, bothmonocotyledonous (e.g. grasses, corn, grains, oat, wheat and barley),dicotyledonous (e.g., Arabidopsis, tobacco, legumes, alfalfa, oaks,eucalyptus, maple), and Gymnosperms (e.g., Scots pine; see Aronen,Finnish Forest Res. Papers, Vol. 595, 1996), white spruce (Ellis et al.,Biotechnology 11:84-89, 1993), and larch (Huang et al., In Vitro Cell27:201-207, 1991).

The plants also include turfgrass, wheat, maize, rice, sugar beet,potato, tomato, lettuce, carrot, strawberry, cassava, sweet potato,geranium, soybean, and various types of woody plants. Woody plantsinclude trees such as palm oak, pine, maple, fir, apple, fig, plum andacacia. Woody plants also include rose and grape vines.

In one embodiment, the DNA constructs of the invention are used totransform woody plants, i.e., trees or shrubs whose stems live for anumber of years and increase in diameter each year by the addition ofwoody tissue. The invention includes methods of transforming plantsincluding eucalyptus and pine species of significance in the commercialforestry industry such as plants selected from the group consisting ofEucalyptus grandis and its hybrids, and Pinus taeda, as well as thetransformed plants and wood and wood pulp derived therefrom. Otherexamples of suitable plants include those selected from the groupconsisting of Pinus banksiana, Pinus brutia, Pinus caribaea, Pinusclausa, Pinus contorta, Pinus coulteri, Pinus echinata, Pinus eldarica,Pinus ellioti, Pinus jeffreyi, Pinus lambertiana, Pinus massoniana,Pinus monticola, Pinus nigra, Pinus palustris, Pinus pinaster, Pinusponderosa, Pinus radiata, Pinus resinosa, Pinus rigida, Pinus serotina,Pinus strobus, Pinus sylvestris, Pinus taeda, Pinus virginiana, Abiesamabilis, Abies balsamea, Abies concolor, Abies grandis, Abieslasiocarpa, Abies magnifica, Abies procera, Chamaecyparis lawsoniona,Chamaecyparis nootkatensis, Chamaecyparis thyoides, Juniperusvirginiana, Larix decidua, Larix laricina, Larix leptolepis, Larixoccidentalis, Larix siberica, Libocedrus decurrens, Picea abies, Piceaengelmanni, Picea glauca, Picea mariana, Picea pungens, Picea rubens,Picea sitchensis, Pseudotsuga menziesii, Sequoia gigantea, Sequoiasempervirens, Taxodium distichum, Tsuga canadensis, Tsuga heterophylla,Tsuga mertensiana, Thuja occidentalis, Thuja plicata, Eucalyptus alba,Eucalyptus bancroftii, Eucalyptus botryoides, Eucalyptus bridgesiana,Eucalyptus calophylla, Eucalyptus camaldulensis, Eucalyptus citriodora,Eucalyptus cladocalyx, Eucalyptus coccifera, Eucalyptus curtisii,Eucalyptus dalrympleana, Eucalyptus deglupta, Eucalyptus delagatensis,Eucalyptus diversicolor, Eucalyptus dunnii, Eucalyptus ficifolia,Eucalyptus globulus, Eucalyptus gomphocephala, Eucalyptus gunnii,Eucalyptus henryi, Eucalyptus laevopinea, Eucalyptus macarthurii,Eucalyptus macrorhyncha, Eucalyptus maculata, Eucalyptus marginata,Eucalyptus megacarpa, Eucalyptus melliodora, Eucalyptus nicholii,Eucalyptus nitens, Eucalyptus nova-angelica, Eucalyptus obliqua,Eucalyptus occidentalis, Eucalyptus obtusiflora, Eucalyptus oreades,Eucalyptus pauciflora, Eucalyptus polybractea, Eucalyptus regnans,Eucalyptus resinifera, Eucalyptus robusta, Eucalyptus rudis, Eucalyptussaligna, Eucalyptus sideroxylon, Eucalyptus stuartiana, Eucalyptustereticornis, Eucalyptus torelliana, Eucalyptus urnigera, Eucalyptusurophylla, Eucalyptus viminalis, Eucalyptus viridis, Eucalyptus wandoo,and Eucalyptus youmanni.

As used herein, the term “plant” also is intended to include the fruit,seeds, flower, strobilus, etc. of the plant. A transformed plant of thecurrent invention can be a direct transfectant, meaning that the DNAconstruct was introduced directly into the plant, such as throughAgrobacterium, or the plant can be the progeny of a transfected plant.The second or subsequent generation plant can be produced by sexualreproduction, i.e., fertilization. Furthermore, the plant can be agametophyte (haploid stage) or a sporophyte (diploid stage).

As used herein, the term “plant tissue” encompasses any portion of aplant, including plant cells. Plant cells include suspension cultures,callus, embryos, meristematic regions, callus tissue, leaves, roots,shoots, gametophytes, sporophytes, pollen, seeds and microspores. Planttissues can be grown in liquid or solid culture, or in soil or suitablemedia in pots, greenhouses or fields. As used herein, “plant tissue”also refers to a clone of a plant, seed, progeny, or propagule, whethergenerated sexually or asexually, and descendents of any of these, suchas cuttings or seeds.

In accordance with one aspect of the invention, a transgenic plant thathas been transformed with a DNA construct of the invention has aphenotype that is different from a plant that has not been transformedwith the DNA construct.

As used herein, “phenotype” refers to a distinguishing feature orcharacteristic of a plant which can be altered according to the presentinvention by integrating one or more DNA constructs of the inventioninto the genome of at least one plant cell of a plant. The DNA constructcan confer a change in the phenotype of a transformed plant by modifyingany one or more of a number of genetic, molecular, biochemical,physiological, morphological, or agronomic characteristics or propertiesof the transformed plant cell or plant as a whole.

In one embodiment, transformation of a plant with a DNA construct of thepresent invention can yield a phenotype including, but not limited toany one or more of increased drought tolerance, herbicide resistance,reduced or increased height, reduced or increased branching, enhancedcold and frost tolerance, improved vigor, enhanced color, enhancedhealth and nutritional characteristics, improved storage, enhancedyield, enhanced salt tolerance, enhanced resistance of the wood todecay, enhanced resistance to fungal diseases, altered attractiveness toinsect pests, enhanced heavy metal tolerance, increased diseasetolerance, increased insect tolerance, increased water-stress tolerance,enhanced sweetness, improved texture, decreased phosphate content,increased germination, increased micronutrient uptake, improved starchcomposition, improved flower longevity, production of novel resins, andproduction of novel proteins or peptides.

In another embodiment, the affected phenotype includes one or more ofthe following traits: propensity to form reaction wood, a reduced periodof juvenility, an increased period of juvenility, self-abscisingbranches, accelerated reproductive development or delayed reproductivedevelopment, as compared to a plant of the same species that has notbeen transformed with the DNA construct.

In a further embodiment, the phenotype that is different in thetransgenic plant includes one or more of the following: lignin quality,lignin structure, wood composition, wood appearance, wood density, woodstrength, wood stiffness, cellulose polymerization, fiber dimensions,lumen size, other plant components, plant cell division, plant celldevelopment, number of cells per unit area, cell size, cell shape, cellwall composition, rate of wood formation, aesthetic appearance of wood,formation of stem defects, average microfibril angle, width of the S2cell wall layer, rate of growth, rate of root formation ratio of root tobranch vegetative development, leaf area index, and leaf shape.

Phenotype can be assessed by any suitable means. The plants can beevaluated based on their general morphology. Transgenic plants can beobserved with the naked eye, can be weighed and their height measured.The plant can be examined by isolating individual layers of planttissue, namely phloem and cambium, which is further sectioned intomeristematic cells, early expansion, late expansion, secondary wallformation, and late cell maturation. See, e.g., Hertzberg, supra. Theplants also can be assessed using microscopic analysis or chemicalanalysis.

Microscopic analysis includes examining cell types, stage ofdevelopment, and stain uptake by tissues and cells. Fiber morphology,such as fiber wall thickness and microfibril angle of wood pulp fiberscan be observed using, for example, microscopic transmissionellipsometry. See Ye and Sundström, Tappi J., 80:181 (1997). Woodstrength, density, and grain slope in wet wood and standing trees can bedetermined by measuring the visible and near infrared spectral data inconjunction with multivariate analysis. See, U.S. Patent ApplicationPublication Nos. 2002/0107644 and 2002/0113212. Lumen size can bemeasured using scanning electron microscopy. Lignin structure andchemical properties can be observed using nuclear magnetic resonancespectroscopy as described in Marita et al., J. Chem. Soc., Perkin Trans.I 2939 (2001).

The biochemical characteristic of lignin, cellulose, carbohydrates andother plant extracts can be evaluated by any standard analytical methodknown including spectrophotometry, fluorescence spectroscopy, HPLC, massspectroscopy, and tissue staining methods.

As used herein, “transformation” refers to a process by which a nucleicacid is inserted into the genome of a plant cell. Such insertionencompasses stable introduction into the plant cell and transmission toprogeny. Transformation also refers to transient insertion of a nucleicacid, wherein the resulting transformant transiently expresses thenucleic acid. Transformation can occur under natural or artificialconditions using various methods well known in the art. Transformationcan be achieved by any known method for the insertion of nucleic acidsequences into a prokaryotic or eukaryotic host cell, includingAgrobacterium-mediated transformation protocols, viral infection,whiskers, electroporation, microinjection, polyethyleneglycol-treatment, heat shock, lipofection, and particle bombardment.Transformation can also be accomplished using chloroplast transformationas described in e.g. Svab et al., Proc. Natl Acad. Sci. 87:8526-30(1990).

In accordance with one embodiment of the invention, transformation inEucalyptus is performed as described in U.S. Patent Application No.60/476,222 (supra) which is incorporated herein by reference in itsentirety. In accordance with another embodiment, transformation of Pinusis accomplished using the methods described in U.S. Patent ApplicationPublication No. 2002/0100083.

Another aspect of the invention provides methods of obtaining woodand/or making wood pulp from a plant transformed with a DNA construct ofthe invention. Methods of producing a transgenic plant are providedabove and are known in the art. A transformed plant can be cultured orgrown under any suitable conditions. For example, pine can be culturedand grown as described in U.S. Patent Application Publication No.2002/0100083. Eucalyptus can be cultured and grown as in, for example,Rydelius, et al., GROWING EUCALYPTUS FOR PULP AND ENERGY, presented atthe Mechanization in Short Rotation, Intensive Culture ForestryConference, Mobile, Ala., 1994. Wood and wood pulp can be obtained fromthe plant by any means known in the art.

As noted above, the wood or wood pulp obtained in accordance with thisinvention may demonstrate improved characteristics including, but notlimited to any one or more of lignin composition, lignin structure, woodcomposition, cellulose polymerization, fiber dimensions, ratio of fibersto other plant components, plant cell division, plant cell development,number of cells per unit area, cell size, cell shape, cell wallcomposition, rate of wood formation, aesthetic appearance of wood,formation of stem defects, rate of growth, rate of root formation ratioof root to branch vegetative development, leaf area index, and leafshape include increased or decreased lignin content, increasedaccessibility of lignin to chemical treatments, improved reactivity oflignin, increased or decreased cellulose content increased dimensionalstability, increased tensile strength, increased shear strength,increased compression strength, increased shock resistance, increasedstiffness, increased or decreased hardness, decreased spirality,decreased shrinkage, and differences in weight, density, and specificgravity.

B. Expression Profiling of Cell Cycle Genes

The present invention also provides methods and tools for performingexpression profiling of cell cycle genes. Expression profiling is usefulin determining whether genes are transcribed or translated, comparingtranscript levels for particular genes in different tissues, genotyping,estimating DNA copy number, determining identity of descent, measuringmRNA decay rates, identifying protein binding sites, determiningsubcellular localization of gene products, correlating gene expressionto a phenotype or other phenomenon, and determining the effect on othergenes of the manipulation of a particular gene. Expression profiling isparticularly useful for identifying gene expression in complex,multigenic events. For this reason, expression profiling is useful incorrelating gene expression to plant phenotype and formation of planttissues and the interconnection thereof to the cell cycle.

Only a small fraction of the genes of a plant's genome are expressed ata given time in a given tissue sample, and all of the expressed genesmay not affect the plant phenotype. To identify genes capable ofaffecting a phenotype of interest, the present invention providesmethods and tools for determining, for example, a gene expressionprofile at a given point in the cell cycle, a gene expression profile ata given point in plant development, and a gene expression profile agiven tissue sample. The invention also provides methods and tools foridentifying cell cycle genes whose expression can be manipulated toalter plant phenotype or to alter the biological activity of cell cyclegene products. In support of these methods, the invention also providesmethods and tools that distinguish expression of different genes of thesame family.

As used herein, “gene expression” refers to the process of transcriptionof a DNA sequence into an RNA sequence, followed by translation of theRNA into a protein, which may or may not undergo post-translationalprocessing. Thus, the relationship between cell cycle stage and/ordevelopmental stage and gene expression can be observed by detecting,quantitatively or qualitatively, changes in the level of an RNA or aprotein. As used herein, the term “biological activity” includes, but isnot limited to, the activity of a protein gene product, including enzymeactivity.

The present invention provides oligonucleotides that are useful in theseexpression profiling methods. Each oligonucleotide is capable ofhybridizing under a given set of conditions to a cell cycle gene or geneproduct. In one aspect of the invention, a plurality of oligonucleotidesis provided, wherein each oligonucleotide hybridizes under a given setof conditions to a different cell cycle gene product. Examples ofoligonucleotides of the present invention include SEQ ID NOs: 471-697.Each of the oligos of SEQ ID NOs 471-697 hybridizes under standardconditions to a different gene product of one of SEQ ID NOs: 1-237. Theoligonucleotides of the invention are useful in determining theexpression of one or more cell cycle genes in any of the above-describedmethods.

1. Cell, Tissue, Nucleic Acid, and Protein Samples

Samples for use in methods of the present invention may be derived fromplant tissue. Suitable plant tissues include, but are not limited to,somatic embryos, pollen, leaves, stems, calli, stolons, microtubers,shoots, xylem, male strolbili, pollen cones, vascular tissue, apicalmeristem, vascular cambium, xylem, root, flower, and seed.

According to the present invention “plant tissue” is used as describedpreviously herein. Plant tissue can be obtained from any of the plantstypes or species described supra.

In accordance with one aspect of the invention, samples are obtainedfrom plant tissue at different stages of the cell cycle, from planttissue at different developmental stages, from plant tissue at varioustimes of the year (e.g. spring versus summer), from plant tissuessubject to different environmental conditions (e.g. variations in lightand temperature) and/or from different types of plant tissue and cells.In accordance with one embodiment, plant tissue is obtained duringvarious stages of maturity and during different seasons of the year. Forexample, plant tissue can be collected from stem dividing cells,differentiating xylem, early developing wood cells, differentiatedspring wood cells, and differentiated summer wood cells. As anotherexample, gene expression in a sample obtained from a plant withdeveloping wood can be compared to gene expression in a sample obtainedfrom a plant which does not have developing wood.

Differentiating xylem includes samples obtained from compression wood,side-wood, and normal vertical xylem. Methods of obtaining samples forexpression profiling from pine and eucalyptus are known. See, e.g.,Allona et al., Proc. Nat'l Acad. Sci. 95:9693-8 (1998) and Whetton etal., Plant Mol. Biol. 47:275-91, and Kirst et al., INT'L UNION OFFORESTRY RESEARCH ORGANIZATIONS BIENNIAL CONFERENCE, S6.8 (June 2003,Umea, Sweden).

In one embodiment of the invention, gene expression in one type oftissue is compared to gene expression in a different type of tissue orto gene expression in the same type of tissue in a difference stage ofdevelopment. Gene expression can also be compared in one type of tissuewhich is sampled at various times during the year (different seasons).For example, gene expression in juvenile secondary xylem can be comparedto gene expression in mature secondary xylem. Similarly, gene expressionin cambium can be compared to gene expression in xylem. Furthermore,gene expression in apical meristems can be compared to gene expressionin cambium.

In an alternative embodiment, differences in gene expression aredetermined as cells from different tissues advance during the cellcycle. In this method, the cells from the different tissues aresynchronized and their gene expression is profiled. Methods ofsynchronizing the stage of cell cycle in a sample are known. Thesemethods include, e.g., cold acclimation, photoperiod, and aphidicoline.See, e.g., Nagata et al., Int. Rev. Cytol. 132:1-30 (1992), Breyne andZabeau, Curr. Opin. Plant Biol. 4:136-42, 140 (2001). A sample isobtained during a specific stage of the cell cycle and gene expressionin that sample is compared to a sample obtained during a different stageof the cell cycle. For example, tissue can be examined in any of thephases of the cell cycle, such as mitosis, G1, G0, S, and G2. Inparticular, one can examine the changes in gene expression at the G1,G2, and metaphase checkpoints.

In another embodiment of the invention, a sample is obtained from aplant having a specific phenotype and gene expression in that sample iscompared to a sample obtained from a plant of the same species that doesnot have that phenotype. For example, a sample can be obtained from aplant exhibiting a fast rate of growth and gene expression can becompared with that of a sample obtained from a plant exhibiting a normalor slow rate of growth. Differentially expressed genes identified fromsuch a comparison can be correlated with growth rate and, therefore,useful for manipulating growth rate.

In a further embodiment, a sample is obtained from clonally propagatedplants. In one embodiment the clonally propagated plants are of thespecies Pinus or Eucalyptus. Individual ramets from the same genotypecan be sacrificed at different times of year. Thus, for any genotypethere can be at least two genetically identical trees sacrificed, earlyin the season and late in the season. Each of these trees can be dividedinto juvenile (top) to mature (bottom) samples. Further, tissue samplescan be divided into, for example, phloem to xylem, in at least 5 layersof peeling. Each of these samples can be evaluated for phenotype andgene expression. See Entry 196.

Where cellular components may interfere with an analytical technique,such as a hybridization assay, enzyme assay, a ligand binding assay, ora biological activity assay, it may be desirable to isolate the geneproducts from such cellular components. Gene products, including nucleicacid and amino acid gene products, can be isolated from cell fragmentsor lysates by any method known in the art.

Nucleic acids used in accordance with the invention can be prepared byany available method or process, or by other processes as they becomeknown in the art. Conventional techniques for isolating nucleic acidsare detailed, for example, in Tijssen, LABORATORY TECHNIQUES INBIOCHEMISTRY AND MOLECULAR BIOLOGY: HYBRIDIZATION WITH NUCLEIC ACIDPROBES, chapter 3 (Elsevier Press, 1993), Berger and Kimmel, MethodsEnzymol. 152:1 (1987), and GIBCO BRL & LIFE TECHNOLOGIES TRIZOL RNAISOLATION PROTOCOL, Form No. 3786 (2000). Techniques for preparingnucleic acid samples, and sequencing polynucleotides from pine andeucalyptus are known. See, e.g., Allona et al., supra and Whetton etal., supra, and U.S. Application No. 60/476,222.

A suitable nucleic acid sample can contain any type of nucleic acidderived from the transcript of a cell cycle gene, i.e., RNA or asubsequence thereof or a nucleic acid for which an mRNA transcribed froma cell cycle gene served as a template. Suitable nucleic acids includecDNA reverse-transcribed from a transcript, RNA transcribed from thatcDNA, DNA amplified from the cDNA, and RNA transcribed from theamplified DNA. Detection of such products or derived products isindicative of the presence and/or abundance of the transcript in thesample. Thus, suitable samples include, but are not limited to,transcripts of the gene or genes, cDNA reverse-transcribed from thetranscript, cRNA transcribed from the cDNA, DNA amplified from thegenes, and RNA transcribed from amplified DNA. As used herein, thecategory of “transcripts” includes but is not limited to pre-mRNAnascent transcripts, transcript processing intermediates, and maturemRNAs and degradation products thereof.

It is not necessary to monitor all types of transcripts to practice theinvention. For example, the expression profiling methods of theinvention can be conducted by detecting only one type of transcript,such as mature mRNA levels only.

In one aspect of the invention, a chromosomal DNA or cDNA library(comprising, for example, fluorescently labeled cDNA synthesized fromtotal cell mRNA) is prepared for use in hybridization methods accordingto recognized methods in the art. See Sambrook et al., supra.

In another aspect of the invention, mRNA is amplified using, e.g., theMessageAmp kit (Ambion). In a further aspect, the mRNA is labeled with adetectable label. For example, mRNA can be labeled with a fluorescentchromophore, such as CyDye (Amersham Biosciences).

In some applications, it may be desirable to inhibit or destroy RNasethat often is present in homogenates or lysates, before use inhybridization techniques. Methods of inhibiting or destroying nucleasesare well known. In one embodiment of the invention, cells or tissues arehomogenized in the presence of chaotropic agents to inhibit nuclease. Inanother embodiment, RNase is inhibited or destroyed by heat treatment,followed by proteinase treatment.

Protein samples can be obtained by any means known in the art. Proteinsamples useful in the methods of the invention include crude celllysates and crude tissue homogenates. Alternatively, protein samples canbe purified. Various methods of protein purification well known in theart can be found in Marshak et al., STRATEGIES FOR PROTEIN PURIFICATIONAND CHARACTERIZATION: A LABORATORY COURSE MANUAL (Cold Spring HarborLaboratory Press 1996).

2. Detecting Level of Gene Expression

For methods of the invention that comprise detecting a level of geneexpression, any method for observing gene expression can be used,without limitation. Such methods include traditional nucleic acidhybridization techniques, polymerase chain reaction (PCR) based methods,and protein determination. The invention includes detection methods thatuse solid support-based assay formats as well as those that usesolution-based assay formats.

Absolute measurements of the expression levels need not be made,although they can be made. The invention includes methods comprisingcomparisons of differences in expression levels between samples.Comparison of expression levels can be done visually or manually, or canbe automated and done by a machine, using for example optical detectionmeans. Subrahmanyam et al., Blood. 97: 2457 (2001); Prashar et al.,Methods Enzymol. 303: 258 (1999). Hardware and software for analyzingdifferential expression of genes are available, and can be used inpracticing the present invention. See, e.g., GenStat Software andGeneExpress® GX Explorer™ Training Manual, supra; Baxevanis &Francis-Ouellette, supra.

In accordance with one embodiment of the invention, nucleic acidhybridization techniques are used to observe gene expression. Exemplaryhybridization techniques include Northern blotting, Southern blotting,solution hybridization, and S1 nuclease protection assays.

Nucleic acid hybridization typically involves contacting anoligonucleotide probe and a sample comprising nucleic acids underconditions where the probe can form stable hybrid duplexes with itscomplementary nucleic acid through complementary base pairing. Forexample, see PCT application WO 99/32660; Berger & Kimmel, MethodsEnzymol. 152: 1 (1987). The nucleic acids that do not form hybridduplexes are then washed away leaving the hybridized nucleic acids to bedetected, typically through detection of an attached detectable label.The detectable label can be present on the probe, or on the nucleic acidsample. In one embodiment, the nucleic acids of the sample aredetectably labeled polynucleotides representing the mRNA transcriptspresent in a plant tissue (e.g., a cDNA library). Detectable labels arecommonly radioactive or fluorescent labels, but any label capable ofdetection can be used. Labels can be incorporated by several approacheddescribed, for instance, in WO 99/32660, supra. In one aspect RNA can beamplified using the MessageAmp kit (Ambion) with the addition ofaminoallyl-UTP as well as free UTP. The aminoallyl groups incorporatedinto the amplified RNA can be reacted with a fluorescent chromophore,such as CyDye (Amersham Biosciences)

Duplexes of nucleic acids are destabilized by increasing the temperatureor decreasing the salt concentration of the buffer containing thenucleic acids. Under low stringency conditions (e.g., low temperatureand/or high salt) hybrid duplexes (e.g., DNA:DNA, RNA:RNA or RNA:DNA)will form even where the annealed sequences are not perfectlycomplementary. Thus, specificity of hybridization is reduced at lowerstringency. Conversely, at higher stringency (e.g., higher temperatureand/or lower salt and/or in the presence of destabilizing reagents)hybridization tolerates fewer mismatches.

Typically, stringent conditions for short probes (e.g., 10 to 50nucleotide bases) will be those in which the salt concentration is atleast about 0.01 to 1.0 M at pH 7.0 to 8.3 and the temperature is atleast about 30° C. Stringent conditions can also be achieved with theaddition of destabilizing agents such as formamide.

Under some circumstances, it can be desirable to perform hybridizationat conditions of low stringency, e.g., 6×SSPE-T (0.9 M NaCl, 60 mMNaH₂PO₄, pH 7.6, 6 mM EDTA, 0.005% Triton) at 37° C., to ensurehybridization. Subsequent washes can then be performed at higherstringency (e.g., 1×SSPE-T at 37° C.) to eliminate mismatched hybridduplexes. Successive washes can be performed at increasingly higherstringency (e.g., down to as low as 0.25×SSPE-T at 37° C. to 50° C.)until a desired level of hybridization specificity is obtained.

In general, standard conditions for hybridization is a compromisebetween stringency (hybridization specificity) and signal intensity.Thus, in one embodiment of the invention, the hybridized nucleic acidsare washed at successively higher stringency conditions and read betweeneach wash. Analysis of the data sets produced in this manner will reveala wash stringency above which the hybridization pattern is notappreciably altered and which provides adequate signal for theparticular oligonucleotide probes of interest. For example, the finalwash may be selected as that of the highest stringency that producesconsistent results and that provides a signal intensity greater thanapproximately 10% of the background intensity.

a. Oligonucleotide Probes

Oligonucleotide probes useful in nucleic acid hybridization techniquesemployed in the present invention are capable of binding to a nucleicacid of complementary sequence through one or more types of chemicalbonds, usually through complementary base pairing via hydrogen bondformation. A probe can include natural bases (i.e., A, G, U, C or T) ormodified bases (7-deazaguanosine, inosine, etc.). In addition, thenucleotide bases in the probes can be joined by a linkage other than aphosphodiester bond, so long as it does not interfere withhybridization. Thus, probes can be peptide nucleic acids in which theconstituent bases are joined by peptide bonds rather than phosphodiesterlinkages.

Oligonucleotide probes can be prepared by any means known in the art.Probes useful in the present invention are capable of hybridizing to anucleotide product of cell cycle genes, such as one of SEQ ID NOs:1-237. Probes useful in the invention can be generated using thenucleotide sequences disclosed in SEQ ID NOs: 1-237. The inventionincludes oligonucleotide probes having at least a 2, 10,15, 20, 30, 35,40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 100 nucleotide fragment of acorresponding contiguous sequence of any one of SEQ ID NOs: 1-237. Theinvention includes oligonucleotides of less than 2, 1, 0.5, 0.1, or 0.05kb in length. In one embodiment, the oligonucleotide is 60 nucleotidesin length.

Oligonucleotide probes can be designed by any means known in the art.See, e.g., Li and Stormo, Bioinformatics 17: 1067-76 (2001).Oligonucleotide probe design can be effected using software. Exemplarysoftware includes ArrayDesigner, GeneScan, and ProbeSelect. Probescomplementary to a defined nucleic acid sequence can be synthesizedchemically, generated from longer nucleotides using restriction enzymes,or can be obtained using techniques such as polymerase chain reaction(PCR). PCR methods are well known and are described, for example, inInnis et al. eds., PCR PROTOCOLS: A GUIDE TO METHODS AND APPLICATIONS,Academic Press Inc. San Diego, Calif. (1990). The probes can be labeled,for example, with a radioactive, biotinylated, or fluorescent tag.Optimally, the nucleic acids in the sample are labeled and the probesare not labeled. Oligonucleotide probes generated by the above methodscan be used in solution or solid support-based methods.

The invention includes oligonucleotide probes that hybridize to aproduct of the coding region or a 3′ untranslated region (3′ UTR) of acell cycle gene. In one embodiment, the oligonucleotide probe hybridizesto the 3′UTR of any one of SEQ ID NOs: 1-237. The 3′ UTR is generally aunique region of the gene, even among members of the same family.Therefore, the probes capable of hybridizing to a product of the 3′ UTRcan be useful for differentiating the expression of individual geneswithin a family where the coding region of the genes likely are highlyhomologous. This allows for the design of oligonucleotide probes to beused as members of a plurality of oligonucleotides, each capable ofuniquely binding to a single gene. In another embodiment, theoligonucleotide probe comprises any one of SEQ ID NOs: 471-697. Inanother embodiment, the oligonucleotide probe consists of any one of SEQID NOs:471-697.

b. Oligonucleotide Array Methods

One embodiment of the invention employs two or more oligonucleotideprobes in combination to detect a level of expression of one or morecell cycle genes, such as the genes of SEQ ID NOs: 1-237. In one aspectof this embodiment, the level of expression of two or more differentgenes is detected. The two or more genes may be from the same ordifferent cell cycle gene families discussed above. Each of the two ormore oligonucleotides may hybridize to a different one of the genes.

One embodiment of the invention employs two or more oligonucleotideprobes, each of which specifically hybridize to a polynucleotide derivedfrom the transcript of a gene provided by SEQ ID NOs: 1-237. Anotherembodiment employs two or more oligonucleotide probes, at least one ofwhich comprises a nucleic acid sequence of SEQ ID NOs: 471-697. Anotherembodiment employs two or more oligonucleotide probes, at least one ofwhich consists of SEQ ID NOs: 471-697.

The oligonucleotide probes may comprise from about 5 to about 60, orfrom about 5 to about 500, nucleotide bases, such as from about 60 toabout 100 nucleotide bases, including from about 15 to about 60nucleotide bases.

One embodiment of the invention uses solid support-based oligonucleotidehybridization methods to detect gene expression. Solid support-basedmethods suitable for practicing the present invention are widely knownand are described, for example, in PCT application WO 95/11755; Huber etal., Anal. Biochem. 299: 24 (2001); Meiyanto et al., Biotechniques. 31:406 (2001); Relogio et al., Nucleic Acids Res. 30:e51 (2002). Any solidsurface to which oligonucleotides can be bound, covalently ornon-covalently, can be used. Such solid supports include filters,polyvinyl chloride dishes, silicon or glass based chips, etc.

One embodiment uses oligonucleotide arrays, i.e. microarrays, which canbe used to simultaneously observe the expression of a number of genes orgene products. Oligonucleotide arrays comprise two or moreoligonucleotide probes provided on a solid support, wherein each probeoccupies a unique location on the support. The location of each probemay be predetermined, such that detection of a detectable signal at agiven location is indicative of hybridization to an oligonucleotideprobe of a known identity. Each predetermined location can contain morethan one molecule of a probe, but each molecule within the predeterminedlocation has an identical sequence. Such predetermined locations aretermed features. There can be, for example, from 2, 10, 100, 1,000,2,000 or 5,000 or more of such features on a single solid support. Inone embodiment, each oligonucleotide is located at a unique position onan array at least 2, at least 3, at least 4, at least 5, at least 6, orat least 10 times.

Oligonucleotide probe arrays for detecting gene expression can be madeand used according to conventional techniques described, for example, inLockhart et al., Nat'l Biotech. 14: 1675 (1996), McGall et al., Proc.Nat'l Acad. Sci. USA 93: 13555 (1996), and Hughes et al., NatureBiotechnol. 19:342 (2001). A variety of oligonucleotide array designs issuitable for the practice of this invention.

In one embodiment the one or more oligonucleotides include a pluralityof oligonucleotides that each hybridize to a different gene expressed ina particular tissue type. For example, the tissue can be developingwood.

In one embodiment, a nucleic acid sample obtained from a plant can beamplified and, optionally labeled with a detectable label. Any method ofnucleic acid amplification and any detectable label suitable for suchpurpose can be used. For example, amplification reactions can beperformed using, e.g. Ambion's MessageAmp, which creates “antisense” RNAor “aRNA” (complementary in nucleic acid sequence to the RNA extractedfrom the sample tissue). The RNA can optionally be labeled using CyDyefluorescent labels. During the amplification step, aaUTP is incorporatedinto the resulting aRNA. The CyDye fluorescent labels are coupled to theaaUTPs in a non-enzymatic reaction. Subsequent to the amplification andlabeling steps, labeled amplified antisense RNAs are precipitated andwashed with appropriate buffer, and then assayed for purity. Forexample, purity can be assay using a NanoDrop spectrophotometer. Thenucleic acid sample is then contacted with an oligonucleotide arrayhaving, attached to a solid substrate (a “microarray slide”),oligonucleotide sample probes capable of hybridizing to nucleic acids ofinterest which may be present in the sample. The step of contacting isperformed under conditions where hybridization can occur between thenucleic acids of interest and the oligonucleotide probes present on thearray. The array is then washed to remove non-specifically bound nucleicacids and the signals from the labeled molecules that remain hybridizedto oligonucleotide probes on the solid substrate are detected. The stepof detection can be accomplished using any method appropriate to thetype of label used. For example, the step of detecting can accomplishedusing a laser scanner and detector. For example, on can use and Axonscanner which optionally uses GenePix Pro software to analyze theposition of the signal on the microarray slide.

Data from one or more microarray slides can analyzed by any appropriatemethod known in the art.

Oligonucleotide probes used in the methods of the present invention,including microarray techniques, can be generated using PCR. PCR primersused in generating the probes are chosen, for example, based on thesequences of SEQ ID NOs:1-237, to result in amplification of uniquefragments of the cell cycle genes (i.e., fragments that hybridize toonly one polynucleotide of any one of SEQ ID NOs: 1-237 under standardhybridization conditions). Computer programs are useful in the design ofprimers with the required specificity and optimal hybridizationproperties. For example, Li and Stormo, supra at 1075, discuss a methodof probe selection using ProbeSelect which selects an optimumoligonucleotide probe based on the entire gene sequence as well as othergene sequences to be probed at the same time.

In one embodiment, oligonucleotide control probes also are used.Exemplary control probes can fall into at least one of three categoriesreferred to herein as (1) normalization controls, (2) expression levelcontrols and (3) negative controls. In microarray methods, one or moreof these control probes may be provided on the array with the inventivecell cycle gene-related oligonucleotides.

Normalization controls correct for dye biases, tissue biases, dust,slide irregularities, malformed slide spots, etc. Normalization controlsare oligonucleotide or other nucleic acid probes that are complementaryto labeled reference oligonucleotides or other nucleic acid sequencesthat are added to the nucleic acid sample to be screened. The signalsobtained from the normalization controls, after hybridization, provide acontrol for variations in hybridization conditions, label intensity,reading efficiency and other factors that can cause the signal of aperfect hybridization to vary between arrays. In one embodiment, signals(e.g., fluorescence intensity or radioactivity) read from all otherprobes used in the method are divided by the signal from the controlprobes, thereby normalizing the measurements.

Virtually any probe can serve as a normalization control. Hybridizationefficiency varies, however, with base composition and probe length.Preferred normalization probes are selected to reflect the averagelength of the other probes being used, but they also can be selected tocover a range of lengths. Further, the normalization control(s) can beselected to reflect the average base composition of the other probesbeing used. In one embodiment, only one or a few normalization probesare used, and they are selected such that they hybridize well (i.e.,without forming secondary structures) and do not match any test probes.In one embodiment, the normalization controls are mammalian genes.

Expression level controls probes hybridize specifically withconstitutively expressed genes present in the biological sample.Virtually any constitutively expressed gene provides a suitable targetfor expression level control probes. Typically, expression level controlprobes have sequences complementary to subsequences of constitutivelyexpressed “housekeeping genes” including, but not limited to certainphotosynthesis genes.

“Negative control” probes are not complementary to any of the testoligonucleotides (i.e., the inventive cell cycle gene-relatedoligonucleotides), normalization controls, or expression controls. Inone embodiment, the negative control is a mammalian gene which is notcomplementary to any other sequence in the sample.

The terms “background” and “background signal intensity” refer tohybridization signals resulting from non-specific binding or otherinteractions between the labeled target nucleic acids (i.e., mRNApresent in the biological sample) and components of the oligonucleotidearray. Background signals also can be produced by intrinsic fluorescenceof the array components themselves.

A single background signal can be calculated for the entire array, or adifferent background signal can be calculated for each target nucleicacid. In a one embodiment, background is calculated as the averagehybridization signal intensity for the lowest 5 to 10 percent of theoligonucleotide probes being used, or, where a different backgroundsignal is calculated for each target gene, for the lowest 5 to 10percent of the probes for each gene. Where the oligonucleotide probescorresponding to a particular cell cycle gene hybridize well and, hence,appear to bind specifically to a target sequence, they should not beused in a background signal calculation. Alternatively, background canbe calculated as the average hybridization signal intensity produced byhybridization to probes that are not complementary to any sequence foundin the sample (e.g., probes directed to nucleic acids of the oppositesense or to genes not found in the sample). In microarray methods,background can be calculated as the average signal intensity produced byregions of the array that lack any oligonucleotides probes at all.

c. PCR-Based Methods

In another embodiment, PCR-based methods are used to detect geneexpression. These methods include reverse-transcriptase-mediatedpolymerase chain reaction (RT-PCR) including real-time and endpointquantitative reverse-transcriptase-mediated polymerase chain reaction(Q-RTPCR). These methods are well known in the art. For example, methodsof quantitative PCR can be carried out using kits and methods that arecommercially available from, for example, Applied BioSystems andStratagene®. See also Kochanowski, QUANTITATIVE PCR PROTOCOLS (HumanaPress, 1999); Innis et al., supra.; Vandesompele et al., Genome Biol. 3:RESEARCH0034 (2002); Stein, Cell Mol. Life Sci. 59: 1235 (2002).

Gene expression can also be observed in solution using Q-RTPCR. Q-RTPCRrelies on detection of a fluorescent signal produced proportionallyduring amplification of a PCR product. See Innis et al., supra. Like thetraditional PCR method, this technique employs PCR oligonucleotideprimers, typically 15-30 bases long, that hybridize to opposite strandsand regions flanking the DNA region of interest. Additionally, a probe(e.g., TaqMan®, Applied Biosystems) is designed to hybridize to thetarget sequence between the forward and reverse primers traditionallyused in the PCR technique. The probe is labeled at the 5′ end with areporter fluorophore, such as 6-carboxyfluorescein (6-FAM) and aquencher fluorophore like 6-carboxy-tetramethyl-rhodamine (TAMRA). Aslong as the probe is intact, fluorescent energy transfer occurs whichresults in the absorbance of the fluorescence emission of the reporterfluorophore by the quenching fluorophore. As Taq polymerase extends theprimer, however, the intrinsic 5′ to 3′ nuclease activity of Taqdegrades the probe, releasing the reporter fluorophore. The increase inthe fluorescence signal detected during the amplification cycle isproportional to the amount of product generated in each cycle.

The forward and reverse amplification primers and internal hybridizationprobe is designed to hybridize specifically and uniquely with onenucleotide derived from the transcript of a target gene. In oneembodiment, the selection criteria for primer and probe sequencesincorporates constraints regarding nucleotide content and size toaccommodate TaqMan® requirements.

SYBR Green® can be used as a probe-less Q-RTPCR alternative to theTaqman®-type assay, discussed above. ABI PRISM® 7900 SEQUENCE DETECTIONSYSTEM USER GUIDE APPLIED BIOSYSTEMS, chap. 1-8, App. A-F. (2002).

A device measures changes in fluorescence emission intensity during PCRamplification. The measurement is done in “real time,” that is, as theamplification product accumulates in the reaction. Other methods can beused to measure changes in fluorescence resulting from probe digestion.For example, fluorescence polarization can distinguish between large andsmall molecules based on molecular tumbling (see U.S. Pat. No.5,593,867).

d. Protein Detection Methods

Proteins can be observed by any means known in the art, includingimmunological methods, enzyme assays and protein array/proteomicstechniques.

Measurement of the translational state can be performed according toseveral protein methods. For example, whole genome monitoring ofprotein—the “proteome”—can be carried out by constructing a microarrayin which binding sites comprise immobilized, preferably monoclonal,antibodies specific to a plurality of proteins having an amino acidsequence of any of SEQ ID NOs: 261-497 or proteins encoded by the genesof SEQ ID NOs:1-237 or conservative variants thereof. See Wildt et al.,Nature Biotechnol. 18: 989 (2000). Methods for making polyclonal andmonoclonal antibodies are well known, as described, for instance, inHarlow & Lane, ANTIBODIES: A LABORATORY MANUAL (Cold Spring HarborLaboratory Press, 1988).

Alternatively, proteins can be separated by two-dimensional gelelectrophoresis systems. Two-dimensional gel electrophoresis iswell-known in the art and typically involves isoelectric focusing alonga first dimension followed by SDS-PAGE electrophoresis along a seconddimension. See, e.g., Hames et al, GEL ELECTROPHORESIS OF PROTEINS: APRACTICAL APPROACH (IRL Press, 1990). The resulting electropherogramscan be analyzed by numerous techniques, including mass spectrometrictechniques, western blotting and immunoblot analysis using polyclonaland monoclonal antibodies, and internal and N-terminal micro-sequencing.

3. Correlating Gene Expression to Phenotype and Tissue Development

As discussed above, the invention provides methods and tools tocorrelate gene expression to plant phenotype. Gene expression may beexamined in a plant having a phenotype of interest and compared to aplant that does not have the phenotype or has a different phenotype.Such a phenotype includes, but is not limited to, increased droughttolerance, herbicide resistance, reduced or increased height, reduced orincreased branching, enhanced cold and frost tolerance, improved vigor,enhanced color, enhanced health and nutritional characteristics,improved storage, enhanced yield, enhanced salt tolerance, enhancedresistance of the wood to decay, enhanced resistance to fungal diseases,altered attractiveness to insect pests, enhanced heavy metal tolerance,increased disease tolerance, increased insect tolerance, increasedwater-stress tolerance, enhanced sweetness, improved texture, decreasedphosphate content, increased germination, increased micronutrientuptake, improved starch composition, improved flower longevity,production of novel resins, and production of novel proteins orpeptides.

In another embodiment, the phenotype includes one or more of thefollowing traits: propensity to form reaction wood, a reduced period ofjuvenility, an increased period of juvenility, self-abscising branches,accelerated reproductive development or delayed reproductivedevelopment.

In a further embodiment, the phenotype that is differs in the plantscompares includes one or more of the following: lignin quality, ligninstructure, wood composition, wood appearance, wood density, woodstrength, wood stiffness, cellulose polymerization, fiber dimensions,lumen size, other plant components, plant cell division, plant celldevelopment, number of cells per unit area, cell size, cell shape, cellwall composition, rate of wood formation, aesthetic appearance of wood,formation of stem defects, average microfibril angle, width of the S2cell wall layer, rate of growth, rate of root formation ratio of root tobranch vegetative development, leaf area index, and leaf shape.

Phenotype can be assessed by any suitable means as discussed above.

In a further embodiment, gene expression can be correlated to a givenpoint in the cell cycle, a given point in plant development, and in agiven tissue sample. Plant tissue can be examined at different stages ofthe cell cycle, from plant tissue at different developmental stages,from plant tissue at various times of the year (e.g. spring versussummer), from plant tissues subject to different environmentalconditions (e.g. variations in light and temperature) and/or fromdifferent types of plant tissue and cells. In accordance with oneembodiment, plant tissue is obtained during various stages of maturityand during different seasons of the year. For example, plant tissue canbe collected from stem dividing cells, differentiating xylem, earlydeveloping wood cells, differentiated spring wood cells, differentiatedsummer wood cells.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the methods and compositionsof the present invention without departing from the spirit or scope ofthe invention. Thus, it is intended that the present invention cover themodifications and variations of this invention provided they come withinthe scope of the appended claims and their equivalents.

The following examples are given to illustrate the present invention. Itshould be understood, however, that the invention is not to be limitedto the specific conditions or details described in these examples.Throughout the specification, any and all references to a publiclyavailable document, including a U.S. patent, are specificallyincorporated by reference.

Examples Example 1

Example 1 illustrates a procedure for RNA extraction and purification,which is particularly useful for RNA obtained from conifer needle,xylem, cambium, and phloem.

Tissue is obtained from conifer needle, xylem, cambium or phloem. Thetissue is frozen in liquid nitrogen and ground. The total RNA isextracted using Concert Plant RNA reagent (Invitrogen). The resultingRNA sample is extracted into phenol:chloroform and treated with DNase.The RNA is then incubated at 65° C. for 2 minutes followed bycentrifugation at 4° C. for 30 minutes. Following centrifugation, theRNA is extracted into phenol at least 10 times to remove contaminants.

The RNA is further cleaned using RNeasy columns (Qiagen). The purifiedRNA is quantified using RiboGreen reagent (Molecular Probes) and purityassessed by gel electrophoresis.

RNA is then amplified using MessageAmp (Ambion). Aminoallyl-UTP and freeUTP are added to the in vitro transcription of the purified RNA at aratio of 4:1 aminoallyl-UTP-to-UTP. The aminoallyl-UTP is incorporatedinto the new RNA strand as it is transcribed. The amino-allyl group isthen reacted with Cy dyes to attach the colorimetric label to theresulting amplified RNA using the Amersham procedure modified for usewith RNA. Unincorporated dye is removed by ethanol precipitation. Thelabeled RNA is quantified spectrophotometrically (NanoDrop). The labeledRNA is fragmented by heating to 95° C. as described in Hughes et al.,Nature Biotechnol. 19:342 (2001).

Example 2

Example 2 illustrates how cell cycle genes important for wooddevelopment in Pinus radiata can be determined and how oligonucleotideswhich uniquely bind to those genes can be designed and synthesized foruse on a microarray.

Pine trees of the species Pinus radiata are grown under natural lightconditions. Tissue samples are prepared as described in, e.g., Sterky etal., Proc. Nat'l Acad. Sci. 95:13330 (1998). Specifically, tissuesamples are collected from woody trees having a height of 5 meters.Tissue samples of the woody trees are prepared by taking tangentialsections through the cambial region of the stem. The stems are sectionedhorizontally into sections ranging from juvenile (top) to mature(bottom). The stem sections separated by stage of development arefurther separated into 5 layers by peeling into sections of phloem,differentiating phloem, cambium, differentiating xylem, developingxylem, and mature xylem. Tissue samples, including leaves, buds, shoots,and roots are also prepared from seedlings of the species Pinus radiata.

RNA is isolated and ESTs generated as described in Example 1 or Sterkyet al., supra. The nucleic acid sequences of ESTs derived from samplescontaining developing wood are compared with nucleic acid sequences ofgenes known to be involved in the plant cell cycle. ESTs from samplesthat do not contain developing wood are also compared with sequences ofgenes known to be involved in the plant cell cycle. An in silicohybridization analysis is performed using BLAST (NCBI). Sequences fromamong the known cell cycle genes that show hybridization in silico toESTs made from samples containing developing wood, but that do nothybridize to ESTs from samples not containing developing wood areselected for further examination.

cDNA clones containing sequences that hybridize to the genes showingwood-preferred expression are selected from cDNA libraries usingtechniques well known in the art of molecular biology. Using thesequence information, oligonucleotides are designed such that eacholigonucleotide is specific for only one cDNA sequence in the library.The oligonucleotide sequences are provided in Table 14. 60-meroligonucleotide probes are designed using the method of Li and Stormo,supra or using software such as ArrayDesigner, GeneScan, andProbeSelect.

The oligonucleotides are then synthesized in situ described in Hughes etal., Nature Biotechnol. 19:324 (2002) or as described in Kane et al.,Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glassslide (Sigma-Genosis, The Woodlands, Tex.) using a 5′ amino linker. Theposition of each oligonucleotide on the slide is known.

Example 3

Example 3 illustrates how cell cycle genes important for wooddevelopment in Eucalyptus grandis can be determined and howoligonucleotides which uniquely bind to those genes can be designed andsynthesized for use on a microarray.

Eucalyptus trees of the species Eucalyptus grandis are grown undernatural light conditions. Tissue samples are prepared as described in,e.g., Sterky et al., Proc. Nat'l Acad. Sci. 95:13330 (1998).Specifically, tissue samples are collected from woody trees having aheight of 5 meters. Tissue samples of the woody trees are prepared bytaking tangential sections through the cambial region of the stem. Thestems are sectioned horizontally into sections ranging from juvenile(top) to mature (bottom). The stem sections separated by stage ofdevelopment are further separated into 5 layers by peeling into sectionsof phloem, differentiating phloem, cambium, differentiating xylem,developing xylem, and mature xylem. Tissue samples, including leaves,buds, shoots, and roots are also prepared from seedlings of the speciesPinus radiata.

RNA is isolated and ESTs generated as described in Example 1 or Sterkyet al., supra. The nucleic acid sequences of ESTs derived from samplescontaining developing wood are compared with nucleic acid sequences ofgenes known to be involved in the plant cell cycle. ESTs from samplesthat do not contain developing wood are also compared with sequences ofgenes known to be involved in the plant cell cycle. An in silicohybridization analysis is performed as described in, for example, Audicand Claverie, Genome Res. 7:986 (1997). Sequences from among the knowncell cycle genes that show hybridization in silico to ESTs made fromsamples containing developing wood, but do not hybridize to ESTs fromsamples not containing developing wood are selected for furtherexamination.

cDNA clones containing sequences that hybridize to the genes showingwood-preferred expression are selected from cDNA libraries usingtechniques well known in the art of molecular biology. Using thesequence information, oligonucleotides are designed such that eacholigonucleotide is specific for only one cDNA sequence in the library.The oligonucleotide sequences are provided in Table 14. 60-meroligonucleotide probes are designed using the method of Li and Stormo,supra or using software such as ArrayDesigner, GeneScan, andProbeSelect.

The oligonucleotides are then synthesized in situ described in Hughes etal., Nature Biotechnol. 19:324 (2002) or as described in Kane et al.,Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glassslide (Sigma-Genosus, The Woodlands, Tex.) using a 5′ amino linker. Theposition of each oligonucleotide on the slide is known.

Example 4

Example 4 illustrates how to detect expression of Pinus radiata cellcycle genes which are important in wood formation using anoligonucleotide microarray prepared as in Example 2. This is an exampleof a balanced incomplete block designed experiment carried out usingaRNA samples prepared from mature-phase phloem (P), cambium (C),expanding xylem found in a layer below the cambium (X1) anddifferentiating, lignifying xylem cells found deeper in the same growthring (X2). In this example, cell cycle gene expression is compared amongthe four samples, namely P, C, X1, and X2.

In the summer, plants of the species Pinus radiata are felled and thebark of the main stem is immediately pulled gently away to reveal thephloem and xylem. The phloem and xylem are then peeled with a scalpelinto separate containers of liquid nitrogen. Needles (leaves) and budsfrom the trees are also harvested with a scalpel into separatecontainers of liquid nitrogen. RNA is subsequently isolated from thefrozen tissue samples as described in Example 1. Equal microgramquantities of total RNA are purified from each sample using RNeasy Minicolumns (Qiagen, Valencia, Calif.) according to the manufacturersinstructions.

Amplification reactions are carried out for each of the P, C, X1, and X2tissue samples. Amplification reactions are performed using Ambion'sMessageAmp kit, a T7-based amplification procedure, following themanufacturer's instructions, except that labeled aaUTP is added to thereagent mix during in the amplification step. aaUTP is incorporated intothe resulting antisense RNA formed during this step. CyDye fluorescentlabels are coupled to the aaUTPs in a non-enzymatic reaction asdescribed in Example 1. Labeled amplified antisense RNAs areprecipitated and washed, and then assayed for purity using a NanoDropspectrophotometer. These labeled antisense RNAs, corresponding to theRNA isolated from the P, C, X1, and X2 tissue samples, constitute thesample nucleic acids, which are referred to as the P, C, X1, and X2samples.

Normalization control samples of known nucleic acids are added to eachsample in a dilution series of 500, 200, 100, 50, 25 and 10 pg/μl forquantitation of the signals. Positive controls corresponding to specificgenes showing expression in all tissues of pine, such as housekeepinggenes, are also added to the plant sample.

Each of four microarray slides is incubated with 125 μL of a P, C, X1 orX2 sample under a coverslip at 42° C. for 16-18 hours. The arrays arewashed in 1×SSC, 0.1% SDS for 10 minutes and then in 0.1×SSC, 0.1% SDSfor 10 minutes and the allowed to dry.

The array slides are scanned using an Axon laser scanner and analyzedusing GenePix Pro software. Data from the microarray slides aresubjected to microarray data analysis using GenStat SAS or Spotfiresoftware. Outliers are removed and ratiometric data for each of thedatasets are normalized using a global normalization which employs acubic spline fit applied to correct for differential dye bias andspatial effects. A second transformation is performed to fit controlsignal ratios to a mean log²=0 (i.e. 1:1 ratio). Normalized data arethen subjected to a variance analysis.

Mean signal intensity for each signal at any given position on themicroarray slide is determined for each of three of P, C, X1, and X2sample microarray slides. This mean signal/probe position is compared tothe signal at the same position on sample slide which was not used forcalculating the mean. For example, a mean signal at a given position isdetermined for P, C, and X1 and the signal at that position in the X2microarray slide is compared to the P, C, and X1 mean signal value.

Table 1 shows genes having greater than doubled signal with any onesample as compared to the mean signal of the other three samples.

TABLE 1 Gene PvCX12 PvX12 CvX12 WD40 repeat protein A −1.24 −0.88 −1.07CDC2 −1.09 −0.78 −0.92 CYCLIN −1.08 −1 −0.26 WD-40 repeat protein B−1.01 −0.87 −0.42 CDC2 −0.83 −0.49 −1.01 P = Phloem C = Cambium X1 =xylem layer-1 X2 = xylem layer-2 PvCX12 = Ratio of the signal for Phloemtarget versus mean signal for Cambium, Xylem1, and Xylem2 targets

The data shows that WD40 repeat protein A encodes a WD40 repeat proteinis less highly expressed in cambium than in developing xylem, while WD40repeat protein B encodes a WD40 repeat protein that is more highlyexpressed in phloem than in the other tissues.

Signal data are then verified with RT-PCR to confirm gene expression inthe target tissue of the genes corresponding to the uniqueoligonucleotides in the probe.

Example 5

Example 5 demonstrates how one can correlate cell cycle gene expressionwith agronomically important wood phenotypes such as density, stiffness,strength, distance between branches, and spiral grain.

Mature clonally propagated pine trees are selected from among theprogeny of known parent trees for superior growth characteristics andresistance to important fungal diseases. The bark is removed from atangential section and the trees are examined for average wood densityin the fifth annual ring at breast height, stiffness and strength of thewood, and spiral grain. The trees are also characterized by theirheight, mean distance between major branches, crown size, and forking.

To obtain seedling families that are segregating for major genes thataffect density, stiffness, strength, distance between branches, spiralgrain and other characteristics that may be linked to any of the genesaffecting these characteristics, trees lacking common parents are chosenfor specific crosses on the criterion that they exhibit the widestvariation from each other with respect to the density, stiffness,strength, distance between branches, and spiral grain criteria. Thus,pollen from a plus tree exhibiting high density, low mean distancebetween major branches, and high spiral grain is used to pollinate conesfrom the unrelated plus tree among the selections exhibiting the lowestdensity, highest mean distance between major branches, and lowest spiralgrain. It is useful to note that “plus trees” are crossed such thatpollen from a plus tree exhibiting high density are used to pollinatedeveloping cones from another plus tree exhibiting high density, forexample, and pollen from a tree exhibiting low mean distance betweenmajor branches would be used to pollinate developing cones from anotherplus tree exhibiting low mean distance between major branches.

Seeds are collected from these controlled pollinations and grown suchthat the parental identity is maintained for each seed and used forvegetative propagation such that each genotype is represented bymultiple ramets. Vegetative propagation is accomplished usingmicropropagation, hedging, or fascicle cuttings. Some ramets of eachgenotype are stored while vegetative propagules of each genotype aregrown to sufficient size for establishment of a field planting. Thegenotypes are arrayed in a replicated design and grown under fieldconditions where the daily temperature and rainfall are measured andrecorded.

The trees are measured at various ages to determine the expression andsegregation of density, stiffness, strength, distance between branches,spiral grain, and any other observable characteristics that may belinked to any of the genes affecting these characteristics. Samples areharvested for characterization of cellulose content, lignin content,cellulose microfibril angle, density, strength, stiffness, tracheidmorphology, ring width, and the like. Samples are also examined for geneexpression as described in Example 4. Ramets of each genotype arecompared to ramets of the same genotype at different ages to establishage:age correlations for these characteristics.

Example 6

Example 6 demonstrates how the stage of plant development and responsesto environmental conditions such as light and season can be correlatedto cell cycle gene expression using microarrays prepared as in Example4. In particular, the changes in gene expression associated with wooddensity are examined.

Trees of three different clonally propagated Eucalyptus grandis hybridgenotypes are grown on a site with a weather station that measures dailytemperatures and rainfall. During the spring and subsequent summer,genetically identical ramets of the three different genotypes are firstphotographed with north-south orientation marks, using photography atsufficient resolution to show bark characteristics of juvenile andmature portions of the plant, and then felled as in Example 4. The ageof the trees is determined by planting records and confirmed by a countof the annual rings. In each of these trees, mature wood is defined asthe outermost rings of the tree below breast height, and juvenile woodas the innermost rings of the tree above breast height. Each tree isaccordingly sectored as follows:

NM—NORTHSIDE MATURE

SM—SOUTHSIDE MATURE

NT—NORTHSIDE TRANSITION

ST—SOUTHSIDE TRANSITION

NJ—NORTHSIDE JUVENILE

SJ—SOUTHSIDE JUVENILE

Tissue is harvested from the plant trunk as well as from juvenile andmature form leaves. Samples are prepared simultaneously for phenotypeanalysis, including plant morphology and biochemical characteristics,and gene expression analysis. The height and diameter of the tree at thepoint from which each sector was taken is recorded, and a soil samplefrom the base of the tree is taken for chemical assay. Samples preparedfor gene expression analysis are weighed and placed into liquid nitrogenfor subsequent preparation of RNA samples for use in the microarrayexperiment. The tissues are denoted as follows:

P—phloem

C—cambium

X1—expanding xylem

X2—differentiating and lignifying xylem

Thin slices in tangential and radial sections from each of the sectorsof the trunk are fixed as described in Ruzin, Plant Microtechnique andMicroscopy, Oxford University Press, Inc., New York, N.Y. (1999) foranatomical examination and confirmation of wood developmental stage.Microfibril angle is examined at the different developmental stages ofthe wood, for example juvenile, transition and mature phases ofEucalyptus grandis wood. Other characteristics examined are the ratio offibers to vessel elements and ray tissue in each sector. Additionally,the samples are examined for characteristics that change betweenjuvenile and mature wood and between spring wood and summer wood, suchas fiber morphology, lumen size, and width of the S2 (thickest) cellwall layer. Samples are further examined for measurements of density inthe fifth ring and determination of modulus of elasticity usingtechniques well known to those skilled in the art of wood assays. See,e.g., Wang, et al., Non-destructive Evaluations of Trees, EXPERIMENTALTECHNIQUES, pp. 28-30 (2000).

For biochemical analysis, 50 grams from each of the harvest samples arefreeze-dried and analyzed, using biochemical assays well known to thoseskilled in the art of plant biochemistry for quantities of simplesugars, amino acids, lipids, other extractives, lignin, and cellulose.See, e.g., Pettersen & Schwandt, J. Wood Chem. & Technol. 11:495 (1991).

In the present example, the phenotypes chosen for comparison are highdensity wood, average density wood, and low density wood. Nucleic acidsamples are prepared as described in Example 3, from trees harvested inthe spring and summer. Gene expression profiling by hybridization anddata analysis is performed as described in Examples 3 and 4.

Using similar techniques and clonally propagated individuals one canexamine cell cycle gene expression as it is related to other complexwood characteristics such as strength, stiffness and spirality.

Example 7

Example 7 demonstrates the ability of the oligonucleotide probes of theinvention to distinguish between highly homologous members of a familyof cell cycle genes. Hybridization to a particular oligonucleotide onthe array identifies a unique WD40 gene that is expressed more stronglyin a genotype having a higher density wood than in observed in othergenotypes examined. The WD40 gene is also expressed more strongly inmature wood than in juvenile wood and more strongly in summer wood thanin spring wood. This gene is not found to be expressed at high levelseither in leaves or buds.

The gene expression pattern is confirmed by RT-PCR. This gene, theputative “density-related” gene, is used for in situ hybridization offixed radial sections. The density-related WD40 gene hybridizes moststrongly to the vascular cambium in regions of the stem where the xylemis comprised primarily of fibers with few vessel elements and few xylemray cells.

These results suggest that the WD40 gene product functions in radialcell division, which occurs in the cambium and results in diametergrowth, rather than in axial cell division such as may be important inthe apex or leaves. Such a gene would be difficult to identify by cDNAmicroarrays or other traditional hybridization means because the highlyconserved regions present in the gene would result in confusing it withgenes encoding enzymes having similar catalytic functions, but acting inaxial or radial divisions. Furthermore, from the sequencesimilarity-based annotation suggesting a function of this gene productin cell division and the observation of this microarray hybridizationpattern, confirmed by RT-PCR and in silico hybridization, this geneproduct functions specifically in developing secondary xylem to guidethe cell division patterns of fibers, such that higher expression ofthis gene results in greater fiber production relative to vessel elementor ray production. The fiber content is correlated with a principalcomponents analysis (PCA) variable that accounts for at least 10% of thevariation in basic density.

Example 8

Example 8 demonstrates how the use of oligonucleotide probes of theinvention can be used to identify one wood “density related” WD40 repeatprotein gene and its promoter from among the family of homologous genes.Further, this example demonstrates how a promoter sequence identifiedusing this method is used to transform other hardwood species to resultin increased diameter growth rates as compared to wild-type plants ofthe same species.

The sequence of the WD40 gene is used to probe a Genome Walker libraryin order to isolate 5′ flanking sequences comprising a promoter region.The promoter region is then operably linked to a beta-glucuronidasereporter gene and cloned into a binary vector for transformation intoEucalyptus using the method described in U.S. Application Ser. No.60/476,222. Regenerated transgenic tobacco and Eucalyptus plants arethen sectioned and stained using X-gluc, demonstrating that themicroarray data results in isolation of a promoter capable of highlycambial-specific expression solely in those portions of the stem thatdevelop more fibers than vessel elements or xylem rays.

Using techniques well known to those skilled in the art of molecularbiology, the promoter is then operably linked to a cell divisionpromoting gene and this construct placed in a binary vector fortransformation into hardwood plants such as Sweetgum and Populus, suchthat the cell division promoting gene is expressed more strongly thannormally in the vascular cambium. This results in increased diametergrowth rate in the transgenic hardwood plants relative to controlhardwood plants.

Example 9

Example 9 demonstrates how a density related polypeptide can be linkedto a tissue-preferred promoter and expressed in pine resulting in aplant with increased wood density.

A density-related polypeptide, which is more highly expressed during theearly spring, is identified by the method described in Example 7. A DNAconstruct having the density-related polypeptide operably linked to apromoter is placed into an appropriate binary vector and transformedinto pine using the method of Connett et al. (U.S. patent applicationSer. Nos. 09/973,088 and 09/973,089). Pine plants are transformed asdescribed in Connett et al., supra, and the transgenic pine plants areused to establish a forest planting. Increased density even in thespring wood (early wood) is observed in the transgenic pine plantsrelative to control pine plants which are not transformed with thedensity related DNA construct.

Example 10

Using techniques well known to those skilled in the art of molecularbiology, the sequence of the putative density-related gene isolated inExample 7 is analyzed in genomic DNA isolated from alfalfa. This enablesthe identification of an orthologue in alfalfa whose sequence is thenused to create an RNAi knockout construct. This construct is thentransformed into alfalfa. See, e.g., Austin et al., Euphytica 85, 3811995. The regenerated transgenic plants show lower fiber content andincreased ray cells content in the xylem. Such properties improveddigestability which results in higher growth rates in cattle fed on thisalfalfa as compared to wild-type alfalfa of the same species.

Example 11

Example 11 demonstrates how gene expression analysis can be used to findgene variants which are present in mature plants having a desirablephenotype. The presence or absence of such a variant can be used topredict the phenotype of a mature plant, allowing screening of theplants at the seedling stage. Although this example employs eucalyptus,the method used herein is also useful in breeding programs for pine andother tree species.

The sequence of a putative density-related gene is used to probe genomicDNA isolated from Eucalyptus that vary in density as described inprevious examples. Non-transgenically produced Eucalyptus hybrids ofdifferent wood phenotypes are examined. One hybrid exhibits high wooddensity and another hybrid exhibits lower wood density. A molecularmarker in the 3′ portion of the coding region is found whichdistinguishes a high-density gene variant from a lower density genevariant.

This molecular marker enables tree breeders to assay non-transgenicEucalyptus hybrids for likely density profiles while the trees are stillat seedling stage, whereas in the absence of the marker, tree breedersmust wait until the trees have grown for multiple years before densityat harvest age can be reliably predicted. This enables selectiveoutplanting of the best trees at seedling stage rather than an expensiveculling operation and resultant erosion at thinning age. This molecularmarker is further useful in the breeding program to determine whichparents will give rise to high density outcross progeny.

Molecular markers found in the 3′ portion of the coding region of thegene that do not correspond to variants seen more frequently in higheror lower wood density non-transgenic Eucalyptus hybrid trees are alsouseful. These markers are found to be useful for fingerprintingdifferent genotypes of Eucalyptus, for use in identity-tracking in thebreeding program and in plantations.

Example 12

This Example describes microarrays for identifying gene expressiondifferences that contribute to the phenotypic characteristics that areimportant in commercial wood, namely wood appearance, stiffness,strength, density, fiber dimensions, coarseness, cellulose and lignincontent, extractives content and the like.

As in Examples 2-4, woody trees of genera that produce commerciallyimportant wood products, in this case Pinus and Eucalyptus, are felledfrom various sites and at various times of year for the collection andisolation of RNA from developing xylem, cambium, phloem, leaves, buds,roots, and other tissues. RNA is also isolated from seedlings of thesame genera.

All contigs are compared to both the ESTs made from RNA isolated fromsamples containing developing wood and the sequences of the ESTs madefrom RNA of various tissues that do not contain developing wood. Contigscontaining primarily ESTs that show more hybridization in silico to ESTsmade from RNA isolated from samples containing developing wood than toESTs made from RNA isolated from samples not containing developing woodare determined to correspond to possible novel genes particularlyexpressed in developing wood. These contigs are then used for BLASTsearches against public domain sequences. Those contigs that hybridizewith high stringency to no known genes or genes annotated as having onlya “hypothetical protein” are selected for the next step. These contigsare considered putative novel genes showing wood-preferred expression.

The longest cDNA clones containing sequences hybridizing to the putativenovel genes showing wood-preferred expression are selected from cDNAlibraries using techniques well known to those skilled in the art ofmolecular biology. The cDNAs are sequenced and full-length gene-codingsequences together with untranslated flanking sequences are obtainedwhere possible. Stretches of 45-80 nucleotides (or oligonucleotides) areselected from each of the sequences of putative novel genes showingwood-preferred expression such that each oligonucleotide probehybridizes at high stringency to only one sequence represented in theESTs made from RNA isolated from trees or seedlings of the same genus.

Oligomers are then chemically synthesized and placed onto a microarrayslide as described in Example 3. Each oligomer corresponds to aparticular sequence of a putative novel gene showing wood-preferredexpression and to no other gene whose sequence is represented among theESTs made from RNA isolated from trees or seedlings of the same genus.

Sample preparation and hybridization are carried out as in Example 4.The technique used in this example is more effective than use of amicroarray using cDNA probes because the presence of a signal representssignificant evidence of the expression of a particular gene, rather thanof any of a number of genes that may contain similarities to the cDNAdue to conserved functional domains or common evolutionary history.Thus, it is possible to differentiate homologous genes, such as those inthe same family, but which may have different functions in phenotypedetermination.

Thus hybridization data, gained using the method of Example 4, enablethe user to identify which of the putative novel genes actually has apattern of coordinate expression with known genes, a pattern ofexpression consistent with a particular developmental role, and/or apattern of expression that suggests that the gene has a promoter thatdrives expression in a valuable way.

The hybridization data thus using this method can be used, for example,to identify a putative novel gene that shows an expression patternparticular to the tracheids with the lowest cellulose microfibril anglein developing spring wood (early wood). The promoter of this gene canalso be isolated as in Example 8, and operably linked to a gene that hasbeen shown as in Example 9 to be associated with late wood (summerwood). Transgenic pine plants containing this construct are generatedusing the methods of Example 9, and the early wood of these plants isthen shown to display several characteristics of late wood, such ashigher microfibril angle, higher density, smaller average lumen size,etc.

Example 13

Example 13 demonstrates the use of a cambium-specific promoterfunctionally linked to a cell cycle gene for increased plant biomass.

Cambium-specific cell cycle transcripts are identified via arrayanalyses of different secondary vasculature layers as described inExample 4. Candidate promoters linked to the genes corresponding tothese transcripts are cloned from pine genomic DNA using, e.g., the BDClontech GenomeWalker kit and tested in transgenic tobacco via areporter assay(s) for cambium specificity/preference. Thecambium-specific promoter overexpressing a cell cycle gene involved insecondary xylem cell division is used to increased wood biomass. Atandem cambium-specific promoter is constructed driving the cell cycleORF. Boosted transcript levels of the candidate cell cycle gene resultin an increased xylem biomass phenotype.

Example 14

Isolation and Characterization of cDNA Clones from Eucalyptus Grandis

Eucalyptus grandis cDNA expression libraries were prepared from matureshoot buds, early wood phloem, floral tissue, leaf tissue (twoindependent libraries), feeder roots, structural roots, xylem or earlywood xylem and were constructed and screened as follows.

Total RNA was extracted from the plant tissue using the protocol ofChang et al. (Plant Molecular Biology Reporter 11:113-116 (1993). mRNAwas isolated from the total RNA preparation using either a Poly(A) QuikmRNA Isolation Kit (Stratagene, La Jolla, Calif.) or Dynal Beads Oligo(dT)₂₅ (Dynal, Skogen, Norway). A cDNA expression library wasconstructed from the purified mRNA by reverse transcriptase synthesisfollowed by insertion of the resulting cDNA clones in Lambda ZAP using aZAP Express cDNA Synthesis Kit (Stratagene), according to themanufacturer's protocol. The resulting cDNAs were packaged using aGigapack II Packaging Extract (Stratagene) using an aliquot (1-5 αl)from the 5 μl ligation reaction dependent upon the library. Massexcision of the library was done using XL1-Blue MRF′ cells and XLOLRcells (Stratagene) with ExAssist helper phage (Stratagene). The excisedphagemids were diluted with NZY broth (Gibco BRL, Gaithersburg, Md.) andplated out onto LB-kanamycin agar plates containing X-gal andisopropylthio-beta-galactoside (IPTG).

Of the colonies plated and selected for DNA miniprep, 99% contained aninsert suitable for sequencing. Positive colonies were cultured in NZYbroth with kanamycin and cDNA was purified by means of alkaline lysisand polyethylene glycol (PEG) precipitation. Agarose gel at 1% was usedto screen sequencing templates for chromosomal contamination. Dye primersequences were prepared using a Turbo Catalyst 800 machine (PerkinElmer/Applied Biosystems Division, Foster City, Calif.) according to themanufacturer's protocol.

DNA sequence for positive clones was obtained using a PerkinElmer/Applied Biosystems Division Prism 377 sequencer. cDNA clones weresequenced first from the 5′ end and, in some cases, also from the 3′end. For some clones, internal sequence was obtained using eitherExonuclease III deletion analysis, yielding a library of differentiallysized subclones in pBK-CMV, or by direct sequencing using gene-specificprimers designed to identified regions of the gene of interest.

The determined cDNA sequences were compared with known sequences in theEMBL database using the computer algorithms FASTA and/or BLASTN.Multiple alignments of redundant sequences were used to build reliableconsensus sequences. Based on similarity to known sequences from otherplant species, the isolated polynucleotide sequences were identified asencoding transcription factors, as detailed herein. The predictedpolypeptide sequences corresponding to the polynucleotide sequences arealso depicted therein.

Example 15

Isolation and Characterization of cDNA Clones from Pinus Radiata

Pinus radiata cDNA expression libraries (prepared from either shoot budtissue, suspension cultured cells, early wood phloem (two independentlibraries), fascicle meristem tissue, male strobilus, root (unknownlineage), feeder roots, structural roots, female strobilus, coneprimordia, female receptive cones and xylem (two independent libraries)were constructed and screened as described above in Example 14.

DNA sequence for positive clones was obtained using forward and reverseprimers on a Perkin Elmer/Applied Biosystems Division Prism 377sequencer and the determined sequences were compared to known sequencesin the database as described above.

Based on similarity to known sequences from other plant species, theisolated polynucleotide sequences were identified as encodingtranscription factors, as detailed herein. The predicted polypeptidesequences corresponding to the polynucleotide sequences are alsodepicted therein.

Example 16

5′ RACE Isolation

To identify additional sequence 5′ or 3′ of a partial cDNA sequence in acDNA library, 5′ and 3′ rapid amplification of cDNA ends (RACE) wasperformed using the SMART RACE cDNA amplification kit (ClontechLaboratories, Palo Alto, Calif.). Generally, the method entailed firstisolating poly(A) mRNA, performing first and second strand cDNAsynthesis to generate double stranded cDNA, blunting cDNA ends, and thenligating of the SMART RACE. Adaptor to the cDNA to form a library ofadaptor-ligated ds cDNA. Gene-specific primers were designed to be usedalong with adaptor specific primers for both 5′ and 3′ RACE reactions.Using 5′ and 3′ RACE reactions, 5′ and 3′ RACE fragments were obtained,sequenced, and cloned. The process may be repeated until 5′ and 3′ endsof the full-length gene were identified. A full-length cDNA maygenerated by PCR using primers specific to 5′ and 3′ ends of the gene byend-to-end PCR.

For example, to amplify the missing 5′ region of a gene fromfirst-strand cDNA, a primer was designed 5′→3′ from the opposite strandof the template sequence, and from the region between ˜100-200 bp of thetemplate sequence. A successful amplification should give an overlap of˜100 bp of DNA sequence between the 5′ end of the template and PCRproduct.

RNA was extracted from four pine tissues, namely seedling, xylem, phloemand structural root using the Concert Reagent Protocol (Invitrogen,Carlsbad, Calif.) and standard isolation and extraction procedures. Theresulting RNA was then treated with DNase, using 10 U/ul DNase I (RocheDiagnostics, Basel, Switzerland). For 100 μg of RNA, 9 μl 10× DNasebuffer (Invitrogen, Carlsbad, Calif.), 10 μl of Roche DNase I and 90 μlof Rnase-free water was used. The RNA was then incubated at roomtemperature for 15 minutes and 1/10 volume 25 mM EDTA is added. A RNeasymini kit (Qiagen, Venlo, The Netherlands) was used for RNA clean upaccording to manufacturer's protocol.

To synthesize cDNA, the extracted RNA from xylem, phloem, seedling androot was used and the SMART RACE cDNA amplification kit (ClontechLaboratories Inc, Palo Alto, Calif.) was followed according tomanufacturer's protocol. For the RACE PCR, the cDNA from the four tissuetypes was combined. The master mix for PCR was created by combiningequal volumes of cDNA from xylem, phloem, root and seedling tissues. PCRreactions were performed in 96 well PCR plates, with 1 μl of primer fromprimer dilution plate (10 mM) to corresponding well positions. 49 μl ofmaster mix is aliquoted into the PCR plate with primers. Thermal cyclingcommenced on a GeneAmp 9700 (Applied Biosystems, Foster City, Calif.) atthe following parameters:

94° C. (5 sec),

72° C. (3 min), 5 cycles;

94° C. (5 sec),

70° C. (10 sec),

72° C. (3 min), 5 cycles;

94° C. (5 sec),

68° C. (10 sec),

72° C. (3 min), 25 cycles.

cDNA was separated on an agarose gel following standard procedures. Gelfragments were excised and eluted from the gel by using the Qiagen96-well Gel Elution kit, following the manufacturer's instructions.

PCR products were ligated into pGEMTeasy (Promega, Madison, Wis.) in a96 well plate overnight according to the following specifications: 60-80ng of DNA, 5 μl 2× rapid ligation buffer, 0.5 μl pGEMT easy vector, 0.1μl DNA ligase, filled to 10 μl with water, and incubated overnight.

Each clone was transformed into E. coli following standard proceduresand DNA was extracted from 12 clones picked by following standardprotocols. DNA extraction and the DNA quality was verified on an 1%agarose gel. The presence of the correct size insert in each of theclones was determined by restriction digests, using the restrictionendonuclease EcoRI, and gel electrophoresis, following standardlaboratory procedures.

Example 17

Curation of an EST Sequence.

During the production of cDNA libraries, the original transcripts ortheir DNA counterparts may have features that prevent them from codingfor functional proteins. There may be insertions, deletions, basesubstitutions, or unspliced or improperly spliced introns. If suchfeatures exist, it is often possible to identify them so that they canbe changed. Similar curation can be performed on any other sequencesthat have homology to sequences in the public databases.

After determination of the DNA sequence, BLAST analysis shows that it isrelated to an Arabidopsis gene on the publicly available Arabidopsisgenome sequence). However, instead of coding for an approximately 240amino acid polypeptide, the consensus being curated is predicted to codefor a product of only 157 amino acid residues, suggesting an error inthe DNA sequence. To identify where the genuine coding region might be,the DNA sequence to the end of each EST is translated in each of thethree reading frames and the predicted sequences are aligned with theArabidopsis gene's amino acid sequence. It is found that the DNA segmentin one portion of the EST codes for a sequence with similarity to thecarboxyl terminus of the Arabidopsis gene. Therefore, it appears that anunspliced intron is present in the EST.

Unspliced introns are a relatively minor issue with regard to use of acloned sequence for overexpression of the gene of interest. The RNAresulting from transcription of the cDNA can be expected to undergonormal processing to remove the intron. Antisense and RNAi constructsare also expected to function to suppress the gene of interest. On otheroccasions, it may be desirable to identify the precise limits of theintron so that it can be removed. When the sequence in question has apublished sequence that is highly similar, it may be possible to findthe intron by aligning the two sequences and identifying the locationswhere the sequence identity falls off, aided by the knowledge thatintrons start with the sequence GT and end with the sequence AG.

When there is some doubt about the site of the intron because highlysimilar sequences are not available, the intron location can be verifiedexperimentally. For example, DNA oligomers can be synthesized flankingthe region where the suspected intron is located. RNA from the sourcespecies, either Pinus or Eucalyptus, is isolated and used as a templateto make cDNA using reverse transcriptase. The selected primers are thenused in a PCR reaction to amplify the correctly spliced DNA segment(predicted size of approximately 350 by smaller than the correspondingsegment of the original consensus) from the population of cDNAs. Theamplified segment is then subjected to sequence analysis and compared tothe consensus sequence to identify the differences.

The same procedure can be used when an alternate splicing event (partialintron remaining, or partial loss of an exon) is suspected. When an ESThas a small change, such as insertion or deletion of a small number ofbases, computer analysis of the EST sequence can still indicate itslocation when a translation product of the wrong size is predicted or ifthere is an obvious frameshift. Verification of the true sequence isdone by synthesis of primers, production of new cDNA, and PCRamplification as described above.

Example 18

Transformation of Populus deltoides with constructs containing cellcycle genes.

Constructs made as described in the preceding example and shown in Table2 below were each inoculated into Agrobacterium cultures by standardtechniques.

Table 2 identifies plasmid(s), genes, and Genesis ID numbers forconstructions described in Example 17.

TABLE 2 Plasmid(s) Gene Genesis ID pGrw14 Cyclin A prga001823 pGrw15Cyclin A prpe001264 pGrw16 Cyclin D prxa004540 pGrw18 Cyclin Dprxl006271 PGrw19 Cyclin D prpb019661 PGrw20 WEE1-like proteinprrd041233

Populus deltoides stock plant cultures were maintained on DKW medium(Driver and Kuniyuki, 1984, McGranahan et al. 1987, availablecommercially from Sigma/Aldrich) with 2.5 uM zeatin in a growth roomwith a 16 h photoperiod. For transformation, petioles were excisedaseptically using a sharp scalpel blade from the stock plants, cut into4-6 mm lengths, placed on DKW medium with 1 ug/ml BAP and 1 ug/ml NAAimmediately after harvest, and incubated in a dark growth chamber (28degrees) for 24 hours.

Agrobacterium cultures containing the desired constructs were grown tolog phase, indicated by an OD600 between 0.8-1.0 A, then pelleted andresuspended in an equal volume of Agrobacterium Induction Medium (AIM),which contains Woody Plant Medium salts (Lloyd, G., and McCown, B.,1981. Woody plant medium. Proc. Intern. Plant Prop. Soc. 30:421,available commercially from Sigma/Aldrich), 5 g/L glucose and 0.6 g/LMES at pH 5.8, with the addition of 1 ul of a 100 mM stock solution ofacetosyringone per ml of AIM. The pellet was resuspended by vortexing.The bacterial cells were incubated for an hour in this medium at 28degrees C. in an environmental chamber, shaking at 100 rpm.

After the induction period, Populus deltoides explants were exposed tothe Agrobacterium mixture for 15 minutes. The explants were then lightlyblotted on sterile paper towels, replaced onto the same plant medium andcultured in the dark at 18-20 degrees C. After a three-dayco-cultivation period, the explants were transferred to DKW medium inwhich the NAA concentration was reduced to 0.1 ug/ml and to which wasadded 400 mg/L timentin to eradicate the Agrobacterium.

After 4 days on eradication medium, explants were transferred to smallmagenta boxes containing the same medium supplemented with timentin (400mg/L) as well as the selection agent geneticin (50 mg/L). Explants weretransferred every two weeks to fresh selection medium. Calli that growin the presence of selection were isolated and sub-cultured to freshselection medium every three weeks. Calli were observed for theproduction of adventitious shoots.

Adventitious shoots were normally observed within two months from theinitiation of transformation. These shoot clusters were transferred toDKW medium to which no NAA was added, and in which the BAP concentrationwas reduced to 0.5 ug.ml, for shoot elongation, typically for about 14weeks. Elongated shoots were excised and transferred to BTM medium(Chalupa, Communicationes Instituti Forestalis Checosloveniae 13:7-39,1983, available commercially from Sigma/Aldrich) at pH5.8, containing 20g/l sucrose and 5 g/l activated charcoal. See Table 3 below.

TABLE 3 Rooting medium for Populus deltoids. BTM-1 Media Components mg/LNH₄NO₃ 412 KNO₃ 475 Ca(NO₃)₂•4H₂O 640 CaCl₂•2H₂O  440* MgSO₄•7H₂O 370KH₂PO₄ 170 MnSO₄•H₂O    2.3 ZnSO₄•7H₂O    8.6 CuSO₄•5H₂O    0.25CoCl₂•6H₂O    0.02 KI    0.15 H₃BO₃    6.2 Na₂MoO₄•2H₂O    0.25FeSO₄•7H₂O   27.8 Na₂EDTA•2H₂O   37.3 Myo-inositol 100 Nicotinic acid   0.5 Pyridoxine HCl    0.5 Thiamine HCl  1 Glycine  2 Sucrose 20000 Activated Carbon 5000 

After development of roots, typically four weeks, transgenic plants werepropagated in the greenhouse by rooted cutting methods, or in vitrothrough axillary shoot induction for four weeks on DKW medium containing11.4 uM zeatin, after which the multiplied shoots were separated andtransferred to root induction medium. Rooted plants were transferred tosoil for evaluation of growth in glasshouse and field conditions.

Example 19

Production of disproportionately large leaves mediated by ectopicexpression of certain cyclin D genes

Approximately 100 explants of Populus deltoides per construct weretransformed with pGRW16 and pGRW19, which contain genes that arenormally show preferred expression in the vasculature, driven by aconstitutive promoter (the Pinus radiata superubiquitin promoter). Uponregeneration, many of the ramets of many of the translines were observedto have disproportionately large leaves relative to control plants. Theleaves were both longer and broader than those of control plants.

Disproportionately large leaves could be a very useful early indicatorof growth potential large leaf size and thus high growth potential. Lageleaf size can be a function of either increased numbers of leaf cells orincreased leaf cell size or both.

Example 20

Production of unusual vascular development mediated by ectopicexpression of a cyclin D gene.

Approximately 100 explants of Populus deltoides per construct weretransformed with pGRW18. Multiple transgenic lines regenerated from thisexperiment showed a very unique pleiotropic phenotype. Leaves of thesetransgenic lines symmetrically folded on both sides of the midrib downthe entire length of the leaf. Many petioles of these lines spiraled,and in many cases turned 360 degrees, in a right-handed fashion towardsthe leaf. The stem showed some thickening and slight bending near themiddle.

One ramet of the transgenic line TDL002534 showing these phenotypes wassacrificed to investigate these aberrancies at the tissue level.Transverse sections of a curling petiole stained with toluidine bluerevealed retardation of vascular development, but the presence ofadditional vascular cylinders developing as indicated by the blackarrows. The xylem and phloem within the vascular cylinders of thecurling petiole appeared to be developmentally similar and spatiallyoriented correctly. Longitudinal sections of straight and curledpetioles may offer an explanation for the spiraling phenomenon. Curledpetioles showed more elongated cells on the outside turn of the curl andmore compressed cells on the opposite side of the petiole.

Perhaps the most striking phenotype was identified in the leaves. Aswith the petioles, aberrant vascular development was noted, comprisingadditional forming vascular cylinders lateral to the larger midrib. Insome sections almost fully-formed veins could be seen immediatelyadjacent to the midrib. In all instances where the folding phenotype wasnoted, this type of leaf configuration was associated with thephenotype.

The development of additional vascular cylinders in the space wherenormally a small number of vascular bundles or a single midrib are seenis indicative of unusual cell division activity at the level of earlyvascular development. Thus, this gene expressed under the control of avascular-preferred promoter rather than a constitutive promoter couldhave utility in increasing cell division in later vascular development,creating additional wood.

Example 21

This example illustrates how polynucleotides important for wooddevelopment in P. radiata can be determined and how oligonucleotideswhich uniquely bind to those genes can be designed and synthesized foruse on a microarray.

Open pollinated trees of approximately 16 years of age are selected fromplantation-grown sites, in the United States for loblolly pine, and inNew Zealand for radiata pine. Trees are felled during the spring andsummer seasons to compare the expression of genes associated with thesedifferent developmental stages of wood formation. Trees are felledindividually and trunk sections are removed from the bottom areaapproximately one to two meters from the base and within one to twometers below the live crown. The section removed from the basal end ofthe trunk contains mature wood. The section removed from below the livecrown contains juvenile wood. Samples collected during the spring seasonare termed earlywood or springwood, while samples collected during thesummer season are considered latewood or summerwood (Larson et al., Gen.Tech. Rep. FPL-GTR-129. Madison, Wis.: U.S. Department of Agriculture,Forest Service, Forest Products Laboratory. p. 42).

Tissues are isolated from the trunk sections such that phloem, cambium,developing xylem, and maturing xylem are removed. These tissues arecollected only from the current year's growth ring. Upon tissue removalin each case, the material is immediately plunged into liquid nitrogento preserve the nucleic acids and other components. The bark is peeledfrom the section and phloem tissue removed from the inner face of thebark by scraping with a razor blade. Cambium tissue is isolated from theouter face of the peeled section by gentle scraping of the surface.Developing xylem and lignifying xylem are isolated by sequentiallyperforming more vigorous scraping of the remaining tissue. Tissues aretransferred from liquid nitrogen into containers for long term storageat −70 until RNA extraction and subsequent analysis is performed.

Example 22

This example illustrates a procedure for RNA extraction andpurification, which is particularly useful for RNA obtained from coniferneedle, xylem, cambium, and phloem.

Tissue is obtained from conifer needle, xylem, cambium or phloem. Thetissue is frozen in liquid nitrogen and ground. The total RNA isextracted using Concert Plant RNA reagent (Invitrogen). The resultingRNA sample is extracted into phenol:chloroform and treated with DNase.The RNA is then incubated at 65° C. for 2 minutes followed bycentrifugation at 4° C. for 30 minutes. Following centrifugation, theRNA is extracted into phenol at least 10 times to remove contaminants.

The RNA is further cleaned using RNeasy columns (Qiagen). The purifiedRNA is quantified using RiboGreen reagent (Molecular Probes) and purityassessed by gel electrophoresis.

RNA is then amplified using MessageAmp (Ambion). Aminoallyl-UTP and freeUTP are added to the in vitro transcription of the purified RNA at aratio of 4:1 aminoallyl-UTP-to-UTP. The aminoallyl-UTP is incorporatedinto the new RNA strand as it is transcribed. The amino-allyl group isthen reacted with Cy dyes to attach the colorimetric label to theresulting amplified RNA using the Amersham procedure modified for usewith RNA. Unincorporated dye is removed by ethanol precipitation. Thelabeled RNA is quantified spectrophotometrically (NanoDrop). The labeledRNA is fragmented by heating to 95° C. as described in Hughes et al.,Nature Biotechnol. 19:342 (2001).

Example 23

This Example illustrates how genes important for wood development in P.radiata can be determined and how oligonucleotides which uniquely bindto those genes can be designed and synthesized for use on a microarray.

Pine trees of the species P. radiata are grown under natural lightconditions. Tissue samples are prepared as described in, e.g., Sterky etal., Proc. Nat'l Acad. Sci. 95:13330 (1998). Specifically, tissuesamples are collected from woody trees having a height of 5 meters.Tissue samples of the woody trees are prepared by taking tangentialsections through the cambial region of the stem. The stems are sectionedhorizontally into sections ranging from juvenile (top) to mature(bottom). The stem sections separated by stage of development arefurther separated into 5 layers by peeling into sections of phloem,differentiating phloem, cambium, differentiating xylem, developingxylem, and mature xylem. Tissue samples, including leaves, buds, shoots,and roots are also prepared from seedlings of the species P. radiata.

RNA is isolated and ESTs generated as described in the Example above orSterky et al., supra. The nucleic acid sequences of ESTs derived fromsamples containing developing wood are compared with nucleic acidsequences of genes known to be involved in polysaccharide synthesis.ESTs from samples that do not contain developing wood are also comparedwith sequences of genes known to be involved in the plant cell cycle. Anin silico hybridization analysis is performed using BLAST (NCBI) asfollows.

Example 24 Eucalyptus in Silico Data

In silico gene expression can be used to determine the membership of theconsensi EST libraries. For each library, a consensus is determined fromthe number of ESTs in any tissue class divided by the total number ofESTs in a class multiplied by 1000. These values provide a normalizedvalue that is not biased by the extent of sequencing from a library.Several libraries were sampled for a consensus value, includingreproductive, bud reproductive, bud vegetative, fruit, leaf, phloem,cambium, xylem, root, stem, sap vegetative, whole plant libraries.

As shown below, a number of the inventive sequences exhibitvascular-preferred expression (more than 50% of the hits by thesesequences if the databases were searched at random would be in librariesmade from developing vascular tissue) and thus are likely to be involvedin wood-related developmental processes. The data are shown in Table 12.

Example 25 Pinus in Silico Data

In silico gene expression can be used to determine the membership of theconsensi EST libraries. For each library, a consensus is determined fromthe number of ESTs in any tissue class divided by the total number ofESTs in a class multiplied by 1000. These values provide a normalizedvalue that is not biased by the extent of sequencing from a library.Several libraries were sampled for a consensus value, including needles,phloem, cambium, xylem, root, stem and, whole plant libraries.

As shown below, a number of the inventive sequences exhibitvascular-preferred expression (more than 50% of the hits by thesesequences if the databases were searched at random would be in librariesmade from developing vascular tissue) and thus are likely to be involvedin wood-related developmental processes. The data are shown in Table 13.

Example 26

Sequences that show hybridization in silico to ESTs made from samplescontaining developing wood, but that do not hybridize to ESTs fromsamples not containing developing wood are selected for furtherexamination.

cDNA clones containing sequences that hybridize to the genes showingwood-preferred expression are selected from cDNA libraries usingtechniques well known in the art of molecular biology. Using thesequence information, oligonucleotides are designed such that eacholigonucleotide is specific for only one cDNA sequence in the library.The oligonucleotide sequences are provided in Table 14. 60-meroligonucleotide probes are designed using the method of Li and Stormo,supra or using software such as ArrayDesigner, GeneScan, andProbeSelect.

The oligonucleotides are then synthesized in situ described in Hughes etal., Nature Biotechnol. 19:324 (2002) or as described in Kane et al.,Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glassslide (Sigma-Genosis, The Woodlands, Tex.) using a 5′ amino linker. Theposition of each oligonucleotide on the slide is known.

Example 27

This example illustrates how to detect expression of Pinus radiata genesof the instant application which are important in wood formation usingan oligonucleotide microarray prepared as described above. This is anexample of a balanced incomplete block designed experiment carried outusing aRNA samples prepared from mature-phase phloem (P), cambium (C),expanding xylem found in a layer below the cambium (X1) anddifferentiating, lignifying xylem cells found deeper in the same growthring (X2). In this example, cell cycle gene expression is compared amongthe four samples, namely P, C, X1, and X2.

In the summer, plants of the species Pinus radiata are felled and thebark of the main stem is immediately pulled gently away to reveal thephloem and xylem. The phloem and xylem are then peeled with a scalpelinto separate containers of liquid nitrogen. Needles (leaves) and budsfrom the trees are also harvested with a scalpel into separatecontainers of liquid nitrogen. RNA is subsequently isolated from thefrozen tissue samples as described in Example 1. Equal microgramquantities of total RNA are purified from each sample using RNeasy Minicolumns (Qiagen, Valencia, Calif.) according to the manufacturersinstructions.

Amplification reactions are carried out for each of the P, C, X1, and X2tissue samples. Amplification reactions are performed using Ambion'sMessageAmp kit, a T7-based amplification procedure, following themanufacturer's instructions, except that labeled aaUTP is added to thereagent mix during in the amplification step. aaUTP is incorporated intothe resulting antisense RNA formed during this step. CyDye fluorescentlabels are coupled to the aaUTPs in a non-enzymatic reaction asdescribed in Example 1. Labeled amplified antisense RNAs areprecipitated and washed, and then assayed for purity using a NanoDropspectrophotometer. These labeled antisense RNAs, corresponding to theRNA isolated from the P, C, X1, and X2 tissue samples, constitute thesample nucleic acids, which are referred to as the P, C, X1, and X2samples.

Normalization control samples of known nucleic acids are added to eachsample in a dilution series of 500, 200, 100, 50, 25 and 10 pg/μl forquantitation of the signals. Positive controls corresponding to specificgenes showing expression in all tissues of pine, such as housekeepinggenes, are also added to the plant sample.

Each of four microarray slides is incubated with 125 μL of a P, C, X1 orX2 sample under a coverslip at 42° C. for 16-18 hours. The arrays arewashed in 1×SSC, 0.1% SDS for 10 minutes and then in 0.1×SSC, 0.1% SDSfor 10 minutes and the allowed to dry.

The array slides are scanned using an Axon laser scanner and analyzedusing GenePix Pro software. Data from the microarray slides aresubjected to microarray data analysis using GenStat SAS or Spotfiresoftware. Outliers are removed and ratiometric data for each of thedatasets are normalized using a global normalization which employs acubic spline fit applied to correct for differential dye bias andspatial effects. A second transformation is performed to fit controlsignal ratios to a mean log²=0 (i.e. 1:1 ratio). Normalized data arethen subjected to a variance analysis.

Mean signal intensity for each signal at any given position on themicroarray slide is determined for each of three of P, C, X1, and X2sample microarray slides. This mean signal/probe position is compared tothe signal at the same position on sample slide which was not used forcalculating the mean. For example, a mean signal at a given position isdetermined for P, C, and X1 and the signal at that position in the X2microarray slide is compared to the P, C, and X1 mean signal value.

Table 5 shows genes having greater than doubled signal with any onesample as compared to the mean signal of the other three samples.

TABLE 5 Gene PvCX12 PvX12 CvX12 WD40 repeat protein A −1.24 −0.88 −1.07CDC2 −1.09 −0.78 −0.92 CYCLIN −1.08 −1 −0.26 WD-40 repeat protein B−1.01 −0.87 −0.42 CDC2 −0.83 −0.49 −1.01 P = Phloem C = Cambium X1 =xylem layer-1 X2 = xylem layer-2 PvCX12 = Ratio of the signal for Phloemtarget versus mean signal for Cambium, Xylem1, and Xylem2 targets

The data shows that WD40 repeat protein A encodes a WD40 repeat proteinis less highly expressed in cambium than in developing xylem, while WD40repeat protein B encodes a WD40 repeat protein that is more highlyexpressed in phloem than in the other tissues.

Signal data are then verified with RT-PCR to confirm gene expression inthe target tissue of the genes corresponding to the uniqueoligonucleotides in the probe.

Example 28

This example illustrates how RNAs of tissues from multiple pine species,in this case both P. radiata and loblolly pine P. taeda trees, areselected for analysis of the pattern of gene expression associated withwood development in the juvenile wood and mature wood forming sectionsof the trees using the microarrays derived from P. radiata cDNAsequences described in Example 4.

Open pollinated trees of approximately 16 years of age are selected fromplantation-grown sites, in the United States for loblolly pine, and inNew Zealand for radiata pine. Trees are felled during the spring andsummer seasons to compare the expression of genes associated with thesedifferent developmental stages of wood formation. Trees are felledindividually and trunk sections are removed from the bottom areaapproximately one to two meters from the base and within one to twometers below the live crown. The section removed from the basal end ofthe trunk contains mature wood. The section removed from below the livecrown contains juvenile wood. Samples collected during the spring seasonare termed earlywood or springwood, while samples collected during thesummer season are considered latewood or summerwood. Larson et al., Gen.Tech. Rep. FPL-GTR-129. Madison, Wis.: U.S. Department of Agriculture,Forest Service, Forest Products Laboratory. p. 42.

Tissues are isolated from the trunk sections such that phloem, cambium,developing xylem, and maturing xylem are removed. These tissues arecollected only from the current year's growth ring. Upon tissue removalin each case, the material is immediately plunged into liquid nitrogento preserve the nucleic acids and other components. The bark is peeledfrom the section and phloem tissue removed from the inner face of thebark by scraping with a razor blade. Cambium tissue is isolated from theouter face of the peeled section by gentle scraping of the surface.Developing xylem and lignifying xylem are isolated by sequentiallyperforming more vigorous scraping of the remaining tissue. Tissues aretransferred from liquid nitrogen into containers for long term storageat −70° C. until RNA extraction and subsequent analysis is performed.

Example 29

This example illustrates procedures alternative to those used in theexample above for RNA extraction and purification, particularly usefulfor RNA obtained from a variety of tissues of woody plants, and aprocedure for hybridization and data analysis using the arrays describedin Example 4.

RNA is isolated according to the protocol of Chang et al., Plant Mol.Biol. Rep. 11:113. DNA is removed using DNase I (Invitrogen, Carlsbad,Calif.) according to the manufacturer's recommendations. The integrityof the RNA samples is determined using the Agilent 2100 Bioanalyzer(Agilent Technologies, USA).

10 μg of total RNA from each tissue is reverse transcribed into cDNAusing known methods.

In the case of Pinus radiata phloem tissue, it can be difficult toextract sufficient amounts of total RNA for normal labelling procedures.Total RNA is extracted and treated as previously described and 100 ng oftotal RNA is amplified using the Ovation™ Nanosample RNA Amplificationsystem from NuGEN™ (NuGEN, CA, USA). Similar amplification kits such asthose manufactured by Ambion may alternatively be used. The amplifiedRNA is reverse transcribed into cDNA and labelled as described above.

Hybridization and stringency washes are performed using the protocol asdescribed in the US Patent Application for “Methods and Kits forLabeling and Hybridizing cDNA for Microarray Analysis” (supra) at 42 C.The arrays (slides) are scanned using a ScanArray 4000 MicroarrayAnalysis System (GSI Lumonics, Ottawa, ON, Canada). Raw, non-normalizedintensity values are generated using QUANTARRAY software (GSI Lumonics,Ottawa, ON, Canada).

A fully balanced, incomplete block experimental design (Kerr andChurchill, Gen. Res. 123:123, 2001) is used in order to design an arrayexperiment that would allow maximum statistical inferences from analyzeddata.

Gene expression data is analyzed using the SAS® Microarray Solutionsoftware package (The SAS Institute, Cary, N.C., USA). Resulting datawas then visualized using JMP® (The SAS Institute, Cary, N.C., USA).

Analysis done for this experiment is an ANOVA approach with mixed modelspecification (Wolfinger et al., J. Comp. Biol. 8:625-637). Two steps oflinear mixed models are applied. The first one, normalization model, isapplied for global normalization at slide-level. The second one, genemodel, is applied for doing rigorous statistical inference on each gene.Both models are stated in Models (1) and (2).

log₂(Y _(ijkls))=θ_(ij) +D _(k) +S _(l) +DS _(kl)+ω_(ijkls)   (1)

R _(ijkls) ^((g))=μ_(ij) ^((g)) +D _(k) ^((g)) +S _(l) ^((g)) +DS _(kl)^((g)) +SS _(ls) ^((g))+ε_(ijkls) ^((g))   (2)

Y_(ijkls) represents the intensity of the s^(th) spot in the 1^(th)slide with the k^(th) dye applying the j^(th) treatment for the i^(th)cell line. θ_(ij), D_(k), S_(l), and D_(Skl) represent the mean effectof the jth treatment in the ith cell line, the kth dye effect, thel^(th) slide random effect, and the random interaction effect of thek^(th) dye in the l^(th) slide. ω_(ijkls) is the stochastic error term.represent the similar roles as θ_(ij), D_(k), S_(l), and D_(Skl) exceptthey are specific for the g^(th) gene. R_(ijkls) ^((g)) represents theresidual of the g^(th) gene from model (1). μ_(ij) ^((g)), D_(k) ^((g)),S_(l) ^((g)), and DS_(kl) ^((g)) represent the similar roles as θ_(ij),D_(k), S_(l), and DS_(kl) except they are specific for the g^(th) gene.SS_(ls) ^((g)) represent the spot by slide random effect for the g^(th)gene. ε_(ijkls) ^((g)) represent the stochastic error term. All randomterms are assumed to be normal distributed and mutually independentwithin each model.

According to the analysis described above, certain cDNAs, some of whichare shown in Table 6 below, are found to be differentially expressed.

TABLE 6 Gene corresponding to SEQ ID Oligo ID Gene_Family Expression 162Pra_000171_O_4 Peptidylprolyl isomerase steady state RNA higher in xylemthan cambium 164 Pra_001480_O_3 Peptidylprolyl isomerase steady stateRNA lower in xylem than cambium control Pra_000218_O_2RIBONUCLEOSIDE-DIPHOSPHATE steady state RNA lower REDUCTASE LARGE CHAIN(EC1.17.4.1). in xylem than cambium control Pra_000193_O_2 PUTATIVESURFACE PROTEIN. steady state RNA lower in xylem than cambium

The involvement of these specific genes in wood development is inferredthrough the association of the up-regulation or down-regulation of genesto the particular stages of wood development. Both the spatial continuumof wood development across a section (phloem, cambium, developing xylem,maturing xylem) at a particular season and tree trunk position and therelationships of season and tree trunk position are considered whenmaking associations of gene expression to the relevance in wooddevelopment.

Example 30

This example demonstrates how one can correlate polysaccharide geneexpression with agronomically important wood phenotypes such as density,stiffness, strength, distance between branches, and spiral grain.

Mature clonally propagated pine trees are selected from among theprogeny of known parent trees for superior growth characteristics andresistance to important fungal diseases. The bark is removed from atangential section and the trees are examined for average wood densityin the fifth annual ring at breast height, stiffness and strength of thewood, and spiral grain. The trees are also characterized by theirheight, mean distance between major branches, crown size, and forking.

To obtain seedling families that are segregating for major genes thataffect density, stiffness, strength, distance between branches, spiralgrain and other characteristics that may be linked to any of the genesaffecting these characteristics, trees lacking common parents are chosenfor specific crosses on the criterion that they exhibit the widestvariation from each other with respect to the density, stiffness,strength, distance between branches, and spiral grain criteria. Thus,pollen from a tree exhibiting high density, low mean distance betweenmajor branches, and high spiral grain is used to pollinate cones fromthe unrelated plus tree among the selections exhibiting the lowestdensity, highest mean distance between major branches, and lowest spiralgrain. It is useful to note that “plus trees” are crossed such thatpollen from a plus tree exhibiting high density are used to pollinatedeveloping cones from another plus tree exhibiting high density, forexample, and pollen from a tree exhibiting low mean distance betweenmajor branches would be used to pollinate developing cones from anotherplus tree exhibiting low mean distance between major branches.

Seeds are collected from these controlled pollinations and grown suchthat the parental identity is maintained for each seed and used forvegetative propagation such that each genotype is represented bymultiple ramets. Vegetative propagation is accomplished usingmicropropagation, hedging, or fascicle cuttings. Some ramets of eachgenotype are stored while vegetative propagules of each genotype aregrown to sufficient size for establishment of a field planting. Thegenotypes are arrayed in a replicated design and grown under fieldconditions where the daily temperature and rainfall are measured andrecorded.

The trees are measured at various ages to determine the expression andsegregation of density, stiffness, strength, distance between branches,spiral grain, and any other observable characteristics that may belinked to any of the genes affecting these characteristics. Samples areharvested for characterization of cellulose content, lignin content,cellulose microfibril angle, density, strength, stiffness, tracheidmorphology, ring width, and the like. RNA is then collected fromreplicated samples of trees showing divergent stiffness and density, orother characteristics, from genotypes that are otherwise as similar aspossible in growth habit, in spring and fall so that early and late wooddevelopment is assayed. These samples are examined for gene expressionsimilarly as described in above examples.

TABLE 7 Concensus ID Information. Patent app SEQ ID Gene FamilyConsensus_ID Expression — control Ribonucleoside- pinusRadiata_000218 upin early spring xylem diphosphate reductase vs late summer xylem CellCycle 168 Peptidylprolyl pinusRadiata_001692 up in juvenile isomerasedeveloping wood vs mature developing xylem — control Nitrite transporterpinusRadiata_016801 up mature developing xylem vs juvenile cambium

Ramets of each genotype are compared to ramets of the same genotype atdifferent ages to establish age:age correlations for thesecharacteristics.

Example 31

Example 8 demonstrates how responses to environmental conditions such aslight and season alter plant phenotype and can be correlated topolysaccharide synthesis gene expression using microarrays. Inparticular, the changes in gene expression associated with wood densityare examined.

Trees of three different clonally propagated E. grandis hybrid genotypesare grown on a site with a weather station that measures dailytemperatures and rainfall. During the spring and subsequent summer,genetically identical ramets of the three different genotypes are firstphotographed with north-south orientation marks, using photography atsufficient resolution to show bark characteristics of juvenile andmature portions of the plant, and then felled. The age of the trees isdetermined by planting records and confirmed by a count of the annualrings. In each of these trees, mature wood is defined as the outermostrings of the tree below breast height, and juvenile wood as theinnermost rings of the tree above breast height. Each tree isaccordingly sectored as follows:

NM—NORTHSIDE MATURE

SM—SOUTHSIDE MATURE

NT—NORTHSIDE TRANSITION

ST—SOUTHSIDE TRANSITION

NJ—NORTHSIDE JUVENILE

SJ—SOUTHSIDE JUVENILE

Tissue is harvested from the plant trunk as well as from juvenile andmature form leaves. Samples are prepared simultaneously for phenotypeanalysis, including plant morphology and biochemical characteristics,and gene expression analysis. The height and diameter of the tree at thepoint from which each sector was taken is recorded, and a soil samplefrom the base of the tree is taken for chemical assay. Samples preparedfor gene expression analysis are weighed and placed into liquid nitrogenfor subsequent preparation of RNA samples for use in the microarrayexperiment. The tissues are denoted as follows:

P—phloem

C—cambium

X1—expanding xylem

X2—differentiating and lignifying xylem

Thin slices in tangential and radial sections from each of the sectorsof the trunk are fixed as described in Ruzin, PLANT MICROTECHNIQUE ANDMICROSCOPY, Oxford University Press, Inc., New York, N.Y. (1999) foranatomical examination and confirmation of wood developmental stage.Microfibril angle is examined at the different developmental stages ofthe wood, for example juvenile, transition and mature phases ofEucalyptus grandis wood. Other characteristics examined are the ratio offibers to vessel elements and ray tissue in each sector. Additionally,the samples are examined for characteristics that change betweenjuvenile and mature wood and between spring wood and summer wood, suchas fiber morphology, lumen size, and width of the S2 (thickest) cellwall layer. Samples are further examined for measurements of density inthe fifth ring and determination of modulus of elasticity usingtechniques well known to those skilled in the art of wood assays. See,e.g., Wang, et al., Non-destructive Evaluations of Trees, EXPERIMENTALTECHNIQUES, pp. 28-30 (2000).

For biochemical analysis, 50 grams from each of the harvest samples arefreeze-dried and analyzed, using biochemical assays well known to thoseskilled in the art of plant biochemistry for quantities of simplesugars, amino acids, lipids, other extractives, lignin, and cellulose.See, e.g., Pettersen & Schwandt, J. Wood Chem. & Technol. 11:495 (1991).

In the present example, the phenotypes chosen for comparison are highdensity wood, average density wood, and low density wood. Nucleic acidsamples are prepared as described in Example 3, from trees harvested inthe spring and summer. Gene expression profiling by hybridization anddata analysis is performed as described above.

Using similar techniques and clonally propagated individuals one canexamine polysaccharide gene expression as it is related to other complexwood characteristics such as strength, stiffness and spirality.

Example 32

Example 32 demonstrates the use of a vascular-preferred promoterfunctionally linked to one of the genes of the instant application.

A vascular-preferred promoter is then linked to one of the genes in theinstant application and used to transform tree species. Boostedtranscript levels of the candidate gene in the xylem of thetransformants results in an increased xylem biomass phenotype.

In another example, a vascular-preferred promoter such as any of thosein ArborGen's November 2003 patent applications is then linked to anRNAi construct containing sequences from one of the genes in the instantapplication and used to transform a tree of the genus from which thegene was isolated. Reduced transcript levels of the candidate gene inthe xylem of the transformants results in an increased xylem biomassphenotype.

Example 33

The vector pARB476 was developed using the following steps. TheBluescript vector (Stratagene, La Jolla, Calif.) was modified by addingthe Superubiquitin 3′UTR and nos 3′terminator sequence at the KpnI andClaI sites to produce the vector pARB005 (SEQ ID NO. 773). To thisvector the P. radiata superubiquitin promoter with intron was added. Thepromoter/intron sequence was first amplified from the P. radiatasuperubiquitin sequence identified in U.S. Pat. No. 6,380,459 usingstandard PCR techniques and the primers of SEQ ID NOS 774 and 775. Theamplified fragment was then ligated into pARB005 using XbaI and PstIrestriction digestion to produce the vector pARB119 (SEQ ID NO. 776).

The poplus tremuloises UDB Glucose binding domain gene (patent WO0071670, ptCelA Genbank number AF072131) was amplified using standardPCR techniques and primers including and ATG and a ClaI site as part ofthe 5′ primer and a TGA and a ClaI site as part of the 3′ primer. Theamplified fragment was then cloned into the ClaI site of pARB119 toproduce the vector pARB476 (SEQ ID NO. 777).

The NotI cassette containing the P. radiata superubiquitin promoter withintron::UDP Glucose Binding domain::3′UTR: nos terminator from pARB476was removed and cloned into the NotI site of pART29 to produce thevector pARB483. The binary vector pART29 is a modified pART27 vector(Gleave, Plant Mol. Biol. 20:1203-1207, 1992) that contains theArabidopsis thaliana ubiquitin 3 (UBQ3) promoter instead of the nos5′promoter and no lacZ sequences.

SEQ ID 773CGATGGGTGTTATTTGTGGATAATAAATTCGGGTGATGTTCAGTGTTTGTCGTATTTCTCACGAATAAATTGTGTTTATGTATGTGTTAGTGTTGTTTGTCTGTTTCAGACCCTCTTATGTTATATTTTTCTTTTCGTCGGTCAGTTGAAGCCAATACTGGTGTCCTGGCCGGCACTGCAATACCATTTCGTTTAATATAAAGACTCTGTTATCCGTGAGCTCGAATTTCCCCGATCGTTCAAACATTTGGCAATAAAGTTTCTTAAGATTGAATCCTGTTGCCGGTCTTGCGATGATTATCATATAATTTCTGTTGAATTACGTTAAGCATGTAATAATTAACATGTAATGCATGACGTTATTTATGAGATGGGTTTTTATGATTAGAGTCCCGCAATTATACATTTAATACGCGATAGAAAACAAAATATAGCGCGCAAACTAGGATAAATTATCGCGCGCGGTGTCATCTATGTTACTAGATCGCGGCCGCATTTAAATGGTACCCAATTCGCCCTATAGTGAGTCGTATTACGCGCGCTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGCTTACAATTTAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCGCGCAATTAACCCTCACTAAAGGGAACAAAAGCTGGGGCCGCTCTAGAACTAGTGGATCCCCCGGGCTGCAGGAATTCGTCCAGCAGTTGTCTGGAGCTCCACCAGAAATCTGGAAGCTTAT SEQID 774 AAATCTAGAGGTACCATTTAAATGCGGCCGCAAAACCCCTCACAAATACATAA SEQ ID 775TTTCTGCAGCTTGAAATTGAAATATGACTAACGAAT SEQ ID 776tctagaggtaccatttaaatgcggccgcaaaacccctcacaaatacataaaaaaaattctttatttaattatcaaactctccactacctttcccaccaaccgttacaatcctgaatgttggaaaaaactaactacattgatataaaaaaactacattacttcctaaatcatatcaaaattgtataaatatatccactcaaaggagtctagaagatccacttggacaaattgcccatagttggaaagatgttcaccaagtcaacaagatttatcaatggaaaaatccatctaccaaacttactttcaagaaaatccaaggattatagagtaaaaaatctatgtattattaagtcaaaaagaaaaccaaagtgaacaaatattgatgtacaagtttgagaggataagacattggaatcgtctaaccaggaggcggaggaattccctagacagttaaaagtggccggaatcccggtaaaaaagattaaaatttttttgtagagggagtgcttgaatcatgttttttatgatggaaatagattcagcaccatcaaaaacattcaggacacctaaaattttgaagtttaacaaaaataacttggatctacaaaaatccgtatcggattttctctaaatataactagaattttcataactttcaaagcaactcctcccctaaccgtaaaacttttcctacttcaccgttaattacattccttaagagtagataaagaaataaagtaaataaaagtattcacaaaccaacaatttatttcttttatttacttaaaaaaacaaaaagtttatttattttacttaaatggcataatgacatatcggagatccctcgaacgagaatcttttatctccctggttttgtattaaaaagtaatttattgtggggtccacgcggagttggaatcctacagacgcgctttacatacgtctcgagaagcgtgacggatgtgcgaccggatgaccctgtataacccaccgacacagccagcgcacagtatacacgtgtcatttctctattggaaaatgtcgttgttatccccgctggtacgcaaccaccgatggtgacaggtcgtctgttgtcgtgtcgcgtagcgggagaagggtctcatccaacgctattaaatactcgccttcaccgcgttacttctcatcttttctcttgcgttgtataatcagtgcgatattctcagagagcttttcattcaaaggtatggagttttgaagggctttactcttaacatttgtttttctttgtaaattgttaatggtggtttctgtgggggaagaatcttttgccaggtccttttgggtttcgcatgtttatttgggttatttttctcgactatggctgacattactagggctttcgtgctttcatctgtgttttcttcccttaataggtctgtctctctggaatatttaattttcgtatgtaagttatgagtagtcgctgtttgtaataggctcttgtctgtaaaggtttcagcaggtgtttgcgttttattgcgtcatgtgtttcagaaggcctttgcagattattgcgttgtactttaatattttgtctccaaccttgttatagtttccctcctttgatctcacaggaaccctttcttctttgagcattttcttgtggcgttctgtagtaatattttaattttgggcccgggttctgagggtaggtgattattcacagtgatgtgctttccctataaggtcctctatgtgtaagctgttagggtttgtgcgttactattgacatgtcacatgtcacatattttcttcctcttatccttcgaactgatggttctttttctaattcgtggattgctggtgccatattttatttctattgcaactgtattttagggtgtctctttctttttgatttcttgttaatatttgtgttcaggttgtaactatgggttgctagggtgtctgccctcttcttttgtgcttctttcgcagaatctgtccgttggtctgtatttgggtgatgaattatttattccttgaagtatctgtctaattagcttgtgatgatgtgcaggtatattcgttagtcatatttcaatttcaagcgatcccccgggctgcaggaattcgtccagcagttgtctggagctccaccagaaatctggaagcttatcgatgggtgttatttgtggataataaattcgggtgatgttcagtgtttgtcgtatttctcacgaataaattgtgtttatgtatgtgttagtgttgtttgtctgtttcagaccctcttatgttatatttttcttttcgtcggtcagttgaagccaatactggtgtcctggccggcactgcaataccatttcgtttaatataaagactctgttatccgtgagctcgaatttccccgatcgttcaaacatttggcaataaagtttcttaagattgaatcctgttgccggtcttgcgatgattatcatataatttctgttgaattacgttaagcatgtaataattaacatgtaatgcatgacgttatttatgagatgggtttttatgattagagtcccgcaattatacatttaatacgcgatagaaaacaaaatatagcgcgcaaactaggataaattatcgcgcgcggtgtcatctatgttactagatcgcggccgcatttaaatggtacccaattcgccctatagtgagtcgtattacgcgcgctcactggccgtcgttttacaacgtcgtgactgggaaaaccctggcgttacccaacttaatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagaggcccgcaccgatcgcccttcccaacagttgcgcagcctgaatggcgaatgggacgcgccctgtagcggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttcccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcgggggctccctttagggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgggccatcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttccaaactggaacaacactcaaccctatctcggtctattcttttgatttataagggattttgccgatttcggcctattggttaaaaaatgagctgatttaacaaaaatttaacgcgaattttaacaaaatattaacgcttacaatttaggtggcacttttcggggaaatgtgcgcggaacccctatttgtttatttttctaaatacattcaaatatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagtatgagtattcaacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctcacccagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttacatcgaactggatctcaacagcggtaagatccttgagagttttcgccccgaagaacgttttccaatgatgagcacttttaaagttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcgccgcatacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatgacagtaagagaattatgcagtgctgccataaccatgagtgataacactgcggccaacttacttctgacaacgatcggaggaccgaaggagctaaccgcttttttgcacaacatgggggatcatgtaactcgccttgatcgttgggaaccggagctgaatgaagccataccaaacgacgagcgtgacaccacgatgcctgtagcaatggcaacaacgttgcgcaaactattaactggcgaactacttactctagcttcccggcaacaattaatagactggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggctggtttattgctgataaatctggagccggtgagcgtgggtctcgcggtatcattgcagcactggggccagatggtaagccctcccgtatcgtagttatctacacgacggggagtcaggcaactatggatgaacgaaatagacagatcgctgagataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatatactttagattgatttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgataatctcatgaccaaaatcccttaacgtgagttttcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgagatcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtttgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaaatactgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgcctacatacctcgctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaagacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttggagcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaagggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccagggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgtgatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggccttttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccgcctttgagtgagctgataccgctcgccgcagccgaacgaccgagcgcagcgagtcagtgagcgaggaagcggaagagcgcccaatacgcaaaccgcctctccccgcgcgttggccgattcattaatgcagctggcacgacaggtttcccgactggaaagcgggcagtgagcgcaacgcaattaatgtgagttagctcactcattaggcaccccaggctttacactttatgcttccggctcgtatgttgtgtggaattgtgagcggataacaatttcacacaggaaacagctatgaccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaagctggggccgctctag SEQ ID 777TCTAGAGGTACCATTTAAATGCGGCCGCAAAACCCCTCACAAATACATAAAAAAAATTCTTTATTTAATTATCAAACTCTCCACTACCTTTCCCACCAACCGTTACAATCCTGAATGTTGGAAAAAACTAACTACATTGATATAAAAAAACTACATTACTTCCTAAATCATATCAAAATTGTATAAATATATCCACTCAAAGGAGTCTAGAAGATCCACTTGGACAAATTGCCCATAGTTGGAAAGATGTTCACCAAGTCAACAAGATTTATCAATGGAAAAATCCATCTACCAAACTTACTTTCAAGAAAATCCAAGGATTATAGAGTAAAAAATCTATGTATTATTAAGTCAAAAAGAAAACCAAAGTGAACAAATATTGATGTACAAGTTTGAGAGGATAAGACATTGGAATCGTCTAACCAGGAGGCGGAGGAATTCCCTAGACAGTTAAAAGTGGCCGGAATCCCGGTAAAAAAGATTAAAATTTTTTTGTAGAGGGAGTGCTTGAATCATGTTTTTTATGATGGAAATAGATTCAGCACCATCAAAAACATTCAGGACACCTAAAATTTTGAAGTTTAACAAAAATAACTTGGATCTACAAAAATCCGTATCGGATTTTCTCTAAATATAACTAGAATTTTCATAACTTTCAAAGCAACTCCTCCCCTAACCGTAAAACTTTTCCTACTTCACCGTTAATTACATTCCTTAAGAGTAGATAAAGAAATAAAGTAAATAAAAGTATTCACAAACCAACAATTTATTTCTTTTATTTACTTAAAAAAACAAAAAGTTTATTTATTTTACTTAAATGGCATAATGACATATCGGAGATCCCTCGAACGAGAATCTTTTATCTCCCTGGTTTTGTATTAAAAAGTAATTTATTGTGGGGTCCACGCGGAGTTGGAATCCTACAGACGCGCTTTACATACGTCTCGAGAAGCGTGACGGATGTGCGACCGGATGACCCTGTATAACCCACCGACACAGCCAGCGCACAGTATACACGTGTCATTTCTCTATTGGAAAATGTCGTTGTTATCCCCGCTGGTACGCAACCACCGATGGTGACAGGTCGTCTGTTGTCGTGTCGCGTAGCGGGAGAAGGGTCTCATCCAACGCTATTAAATACTCGCCTTCACCGCGTTACTTCTCATCTTTTCTCTTGCGTTGTATAATCAGTGCGATATTCTCAGAGAGCTTTTCATTCAAAGGTATGGAGTTTTGAAGGGCTTTACTCTTAACATTTGTTTTTCTTTGTAAATTGTTAATGGTGGTTTCTGTGGGGGAAGAATCTTTTGCCAGGTCCTTTTGGGTTTCGCATGTTTATTTGGGTTATTTTTCTCGACTATGGCTGACATTACTAGGGCTTTCGTGCTTTCATCTGTGTTTTCTTCCCTTAATAGGTCTGTCTCTCTGGAATATTTAATTTTCGTATGTAAGTTATGAGTAGTCGCTGTTTGTAATAGGCTCTTGTCTGTAAAGGTTTCAGCAGGTGTTTGCGTTTTATTGCGTCATGTGTTTCAGAAGGCCTTTGCAGATTATTGCGTTGTACTTTAATATTTTGTCTCCAACCTTGTTATAGTTTCCCTCCTTTGATCTCACAGGAACCCTTTCTTCTTTGAGCATTTTCTTGTGGCGTTCTGTAGTAATATTTTAATTTTGGGCCCGGGTTCTGAGGGTAGGTGATTATTCACAGTGATGTGCTTTCCCTATAAGGTCCTCTATGTGTAAGCTGTTAGGGTTTGTGCGTTACTATTGACATGTCACATGTCACATATTTTCTTCCTCTTATCCTTCGAACTGATGGTTCTTTTTCTAATTCGTGGATTGCTGGTGCCATATTTTATTTCTATTGCAACTGTATTTTAGGGTGTCTCTTTCTTTTTGATTTCTTGTTAATATTTGTGTTCAGGTTGTAACTATGGGTTGCTAGGGTGTCTGCCCTCTTCTTTTGTGCTTCTTTCGCAGAATCTGTCCGTTGGTCTGTATTTGGGTGATGAATTATTTATTCCTTGAAGTATCTGTCTAATTAGCTTGTGATGATGTGCAGGTATATTCGTTAGTCATATTTCAATTTCAAGCGATCCCCCGGGCTGCAGGAATTCGTCCAGCAGTTGTCTGGAGCTCCACCAGAAATCTGGAAGCTTATCGATATGGATCAGTTCCCCAAGTGGAATCCTGTCAATAGAGAAACGTATATCGAAAGGCTGTCGGCAAGGTATGAAAGAGAGGGTGAGCCTTCTCAGCTTGCTGGTGTGGATTTTTTCGTGAGTACTGTTGATCCGCTGAAGGAACCGCCATTGATCACTGCCAATACAGTCCTTTCCATCCTTGCTGTGGACTATCCCGTCGATAAAGTCTCCTGCTACGTGTCTGATGATGGTGCAGCTATGCTTTCATTTGAATCTCTTGTAGAAACAGCTGAGTTTGCAAGGAAGTGGGTTCCGTTCTGCAAAAAATTCTCAATTGAACCAAGAGCACCGGAGTTTTACTTCTCACAGAAAATTGATTACTTGAAAGACAAGGTTCAACCTTCTTTCGTGAAAGAACGTAGAGCAATGAAAAGGGATTATGAAGAGTACAAAGTCCGAGTTAATGCCCTGGTAGCAAAGGCTCAGAAAACACCTGAAGAAGGATGGACTATGCAAGATGGAACACCTTGGCCTGGGAATAACACACGTGATCACCCTGGCATGATTCAGGTCTTCCTTGGAAATACTGGAGCTCGTGACATTGAAGGAAATGAACTACCTCGTCTAGTATATGTCTCCAGGGAGAAGAGACCTGGCTACCAGCACCACAAAAAGGCTGGTGCAGAAAATGCTCTGGTGAGAGTGTCTGCAGTACTCACAAATGCTCCCTACATCCTCAATGTTGATTGTGATCACTATGTAAACAATAGCAAGGCTGTTCGAGAGGCAATGTGCATCCTGATGGACCCACAAGTAGGTCGAGATGTATGCTATGTGCAGTTCCCTCAGAGGTTTGATGGCATAGATAAGAGTGATCGCTACGCCAATCGTAACGTAGTTTTCTTTGATGTTAACATGAAAGGGTTGGATGGCATTCAAGGACCAGTATACGTAGGAACTGGTTGTGTTTTCAACAGGCAAGCACTTTACGGCTACGGGCCTCCTTCTATGCCCAGCTTACGCAAGAGAAAGGATTCTTCATCCTGCTTCTCATGTTGCTGCCCCTCAAAGAAGAAGCCTGCTCAAGATCCAGCTGAGGTATACAGAGATGCAAAAAGAGAGGATCTCAATGCTGCCATATTTAATCTTACAGAGATTGATAATTATGACGAGCATGAAAGGTCAATGCTGATCTCCCAGTTGAGCTTTGAGAAAACTTTTGGCTTATCTTCTGTCTTCATTGAGTCTACACTAATGGAGAATGGAGGAGTACCCGAGTCTGCCAACTCACCAACACTCATCAAGGAAGCAATTCATGTCATCGGCTGTGGCTATGAAGAGAAGACTGAATGGGGAAAAGAGATTGGTTGGATATATGGGTCAGTCACTGAGGATATCTTAAGTGGCTTCAAGATGCACTGCCGAGGATGGAGATCAATTTACTGCATGCCCGTAAGGCCTGCATTCAAAGGATCTGCACCCATCAACCTGTCTGATAGATTGCACCAGGTCCTCCGATGGGCTCTTGGTTCTGTGGAAATTTTCTTTAGCAGACACTGTCCCCTCTGGTACGGGTTTGGAGGAGGCCGTCTTAAATGGCTCCAAAGGCTTGCGTATATAAACACCATTGTGTACCCATGAATCGATGGGTGTTATTTGTGGATAATAAATTCGGGTGATGTTCAGTGTTTGTCGTATTTCTCACGAATAAATTGTGTTTATGTATGTGTTAGTGTTGTTTGTCTGTTTCAGACCCTCTTATGTTATATTTTTCTTTTCGTCGGTCAGTTGAAGCCAATACTGGTGTCCTGGCCGGCACTGCAATACCATTTCGTTTAATATAAAGACTCTGTTATCCGTGAGCTCGAATTTCCCCGATCGTTCAAACATTTGGCAATAAAGTTTCTTAAGATTGAATCCTGTTGCCGGTCTTGCGATGATTATCATATAATTTCTGTTGAATTACGTTAAGCATGTAATAATTAACATGTAATGCATGACGTTATTTATGAGATGGGTTTTTATGATTAGAGTCCCGCAATTATACATTTAATACGCGATAGAAAACAAAATATAGCGCGCAAACTAGGATAAATTATCGCGCGCGGTGTCATCTATGTTACTAGATCGCGGCCGCATTTAAATGGTACCCAATTCGCCCTATAGTGAGTCGTATTACGCGCGCTCACTGGCCGTCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGCTTACAATTTAGGTGGCACTTTTCGGGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACGCCAAGCGCGCAATTAACCCTCACTAAAGGGAACAAAAGCTGGGGCCGCTCTAG

TABLE 8 pGrowth Information. CW AR Plasmid(s) Promoter Gene Genesis ID88 pGrowth14 SUBIN Cyclin A prga001823 88 pGrowth15 SUBIN Cyclin Aprpe001264 88 pGrowth16 SUBIN Cyclin D prxa004540 88 pGrowth18 SUBINCyclin D prxl006271 88 pGrowth19 SUBIN Cyclin D prpb019661 88 pGrowth20SUBIN WEE1-like protein prrd041233

To make the growth100 plasmids, an acceptor vector (pWVK202) was builtby first inserting the NotI-SUBIN::UDPGBD::nos term-NotI cassette frompARB483a into plasmid pWVK147 at NotI. Next, the UDPGBD gene was removedusing restriction sites PstI and ClaI. A polylinker containing therestriction sites PstI, NheI, AvrII, ScaI, and ClaI was inserted inplace of the UDPGBD gene. Sites AvrII and NheI are both compatible withSpeI, a site found often in the plasmids provided by Genesis. ScaI isblunt, so any fragment can be blunted and then inserted at that positioninto the acceptor vector. Plasmids were received from Genesis andanalyzed to determine which restriction sites would be most suitable forsubcloning into the acceptor vector pWVK202. After the ligations wereperformed, the resulting products were checked by extensive restrictiondigest analysis to make sure that the desired plasmid had been created.

TABLE 9 Eucalyptus grandis Cell Cycle Genes and Proteins. Patent PatentDNA SEQ Protein SEQ ORF ORF ID NO ID NO Sequence Identifier start stop 1236 eucalyptusSpp_003910 387 1820 2 237 eucalyptusSpp_019213 99 1007 3238 eucalyptusSpp_036800 120 1004 4 239 eucalyptusSpp_040260 23 937 5240 eucalyptusSpp_041965 149 1033 6 241 eucalyptusSpp_002906 199 1116 7242 eucalyptusSpp_001518 41 982 8 243 eucalyptusSpp_008078 291 2042 9244 eucalyptusSpp_009826 107 2236 10 245 eucalyptusSpp_010364 82 1749 11246 eucalyptusSpp_011523 151 1560 12 247 eucalyptusSpp_024358 82 1644 13248 eucalyptusSpp_039125 626 2782 14 249 eucalyptusSpp_005362 13 1467 15250 eucalyptusSpp_044857 113 1558 16 251 eucalyptusSpp_001743 187 168617 252 eucalyptusSpp_012405 238 1653 18 253 eucalyptusSpp_003739 2351539 19 254 eucalyptusSpp_022338 158 1618 20 255 eucalyptusSpp_028605205 1530 21 256 eucalyptusSpp_041006 174 1499 22 257eucalyptusSpp_006643 94 1332 23 258 eucalyptusSpp_045338 176 1342 24 259eucalyptusSpp_046486 150 1283 25 260 eucalyptusSpp_012070 101 367 26 261eucalyptusSpp_006617 9 1352 27 262 eucalyptusSpp_007827 89 1486 28 263eucalyptusSpp_008036 80 1477 29 264 010212EGLA007017HT 160 1062 30 265eucalyptusSpp_001596 172 1077 31 266 eucalyptusSpp_005870 66 989 32 267eucalyptusSpp_006901 111 1541 33 268 eucalyptusSpp_006902 116 1615 34269 eucalyptusSpp_007440 155 1453 35 270 eucalyptusSpp_008994 228 203336 271 eucalyptusSpp_024580 110 1258 37 272 eucalyptusSpp_037831 50 146238 273 eucalyptusSpp_034958 176 739 39 274 001209EGXC004488HT 150 152940 275 010310EGXD012820HT 247 1971 41 276 010310EGXD013036HT 136 1644 42277 010316EGXF999037HT 48 836 43 278 010324EGXF002118HT 49 822 44 279011019EGKA001923HT 185 751 45 280 eucalyptusSpp_000966 103 621 46 281eucalyptusSpp_001037 41 559 47 282 eucalyptusSpp_004603 127 693 48 283eucalyptusSpp_005465 28 639 49 284 eucalyptusSpp_006571 135 812 50 285eucalyptusSpp_006786 119 613 51 286 eucalyptusSpp_007057 38 562 52 287eucalyptusSpp_008670 109 1872 53 288 eucalyptusSpp_009137 74 1159 54 289eucalyptusSpp_010285 54 2045 55 290 eucalyptusSpp_010600 53 1879 56 291eucalyptusSpp_011551 7 690 57 292 eucalyptusSpp_020743 83 601 58 293eucalyptusSpp_023739 125 535 59 294 eucalyptusSpp_024103 55 573 60 295eucalyptusSpp_031985 147 842 61 296 eucalyptusSpp_032025 167 487 62 297eucalyptusSpp_032173 195 890 63 298 eucalyptusSpp_033340 68 586 64 299eucalyptusSpp_009143 182 3265 65 300 eucalyptusSpp_000349 165 1145 66301 eucalyptusSpp_000575 529 1569 67 302 eucalyptusSpp_000804 156 113668 303 eucalyptusSpp_000805 90 1073 69 304 eucalyptusSpp_000806 66 104970 305 eucalyptusSpp_002248 277 1512 71 306 eucalyptusSpp_003203 33 107672 307 eucalyptusSpp_003209 65 973 73 308 eucalyptusSpp_004429 82 104774 309 eucalyptusSpp_004607 43 1101 75 310 eucalyptusSpp_004682 142 109576 311 eucalyptusSpp_005786 61 1257 77 312 eucalyptusSpp_005887 193 152778 313 eucalyptusSpp_005981 109 1155 79 314 eucalyptusSpp_006766 71 121380 315 eucalyptusSpp_006769 109 1785 81 316 eucalyptusSpp_006907 3642685 82 317 eucalyptusSpp_007518 96 1412 83 318 eucalyptusSpp_007717 1161702 84 319 eucalyptusSpp_007718 46 1101 85 320 eucalyptusSpp_007741 231258 86 321 eucalyptusSpp_007884 404 2644 87 322 eucalyptusSpp_008258107 2383 88 323 eucalyptusSpp_008465 243 1625 89 324eucalyptusSpp_008616 126 1127 90 325 eucalyptusSpp_008690 257 1390 91326 eucalyptusSpp_008708 178 1632 92 327 eucalyptusSpp_008850 290 291793 328 eucalyptusSpp_009072 148 1197 94 329 eucalyptusSpp_009465 1401567 95 330 eucalyptusSpp_009472 376 1737 96 331 eucalyptusSpp_009550 691010 97 332 eucalyptusSpp_010284 149 1423 98 333 eucalyptusSpp_010595365 2677 99 334 eucalyptusSpp_010657 24 923 100 335 eucalyptusSpp_012636221 3598 101 336 eucalyptusSpp_012748 44 1447 102 337eucalyptusSpp_012879 196 1314 103 338 eucalyptusSpp_015515 193 1668 104339 eucalyptusSpp_015724 78 1634 105 340 eucalyptusSpp_016167 85 2826106 341 eucalyptusSpp_016633 74 1246 107 342 eucalyptusSpp_017485 1004377 108 343 eucalyptusSpp_018007 58 2439 109 344 eucalyptusSpp_020775159 1064 110 345 eucalyptusSpp_023132 118 1665 111 346eucalyptusSpp_023569 57 1628 112 347 eucalyptusSpp_023611 250 1566 113348 eucalyptusSpp_024934 106 1434 114 349 eucalyptusSpp_025546 190 1917115 350 eucalyptusSpp_030134 102 2942 116 351 eucalyptusSpp_031787 751079 117 352 eucalyptusSpp_034435 99 1148 118 353 eucalyptusSpp_034452232 1806 119 354 eucalyptusSpp_035789 72 1124 120 355eucalyptusSpp_035804 315 2069 121 356 eucalyptusSpp_043057 145 1968 122357 eucalyptusSpp_046741 130 1488 123 358 eucalyptusSpp_047161 269 1693698 718 eucalyptusSpp_008994 699 719 eucalyptusSpp_009143 700 720eucalyptusSpp_006366 701 721 eucalyptusSpp_006907 702 722eucalyptusSpp_012636 703 723 eucalyptusSpp_015724 704 724eucalyptusSpp_016167 705 725 eucalyptusSpp_017485 706 726eucalyptusSpp_030134 707 727 eucalyptusSpp_046741 708 728eucalyptusSpp_047161 709 729 eucalyptusSpp_017378

TABLE 10 Pinus radiata cell cycle genes and proteins. Patent Patent DNASEQ Protein SEQ ORF ORF ID NO ID NO Sequence Identifier start stop 124359 pinusRadiata_001766 1163 2545 125 360 pinusRadiata_002927 152 1582126 361 990309PRCA009171HT 389 1297 127 362 pinusRadiata_013714 38 946128 363 pinusRadiata_016332 180 1088 129 364 pinusRadiata_021677 40 948130 365 pinusRadiata_027562 229 1134 131 366 pinusRadiata_001504 1052642 132 367 pinusRadiata_015211 187 2580 133 368 pinusRadiata_020421220 1749 134 369 pinusRadiata_003187 438 1748 135 370pinusRadiata_015661 240 1631 136 371 pinusRadiata_013874 252 1604 137372 pinusRadiata_014615 261 1817 138 373 pinusRadiata_004578 167 1576139 374 pinusRadiata_023387 183 1598 140 375 pinusRadiata_006970 98 1126141 376 pinusRadiata_010322 148 894 142 377 pinusRadiata_022721 287 1363143 378 pinusRadiata_023407 251 1348 144 379 pinusRadiata_001945 229 510145 380 pinusRadiata_008233 92 409 146 381 pinusRadiata_008234 64 381147 382 pinusRadiata_022054 68 349 148 383 pinusRadiata_012137 125 1849149 384 pinusRadiata_012582 70 1602 150 385 pinusRadiata_015285 140 1465151 386 pinusRadiata_017229 628 2565 152 387 pinusRadiata_020724 55 1818153 388 pinusRadiata_004555 259 1710 154 389 pinusRadiata_004556 3561807 155 390 pinusRadiata_005729 261 1298 156 391 pinusRadiata_007395365 2251 157 392 pinusRadiata_009503 156 1454 158 393pinusRadiata_011283 203 1348 159 394 pinusRadiata_012322 229 1644 160395 pinusRadiata_018671 156 1454 161 396 pinusRadiata_023236 27 2222 162397 pinusRadiata_000171 71 1759 163 398 pinusRadiata_000172 358 2040 164399 pinusRadiata_001480 238 756 165 400 pinusRadiata_001481 285 803 166401 pinusRadiata_001483 190 708 167 402 pinusRadiata_001484 156 674 168403 pinusRadiata_001692 176 1912 169 404 pinusRadiata_005313 64 765 170405 pinusRadiata_006362 93 881 171 406 pinusRadiata_006493 372 1070 172407 pinusRadiata_006983 28 594 173 408 pinusRadiata_006984 34 648 174409 pinusRadiata_007665 481 1611 175 410 pinusRadiata_012196 93 584 176411 pinusRadiata_013382 250 1869 177 412 pinusRadiata_016461 84 422 178413 pinusRadiata_017611 128 1213 179 414 pinusRadiata_019776 265 837 180415 pinusRadiata_020659 38 781 181 416 pinusRadiata_022559 38 526 182417 pinusRadiata_024188 37 1158 183 418 pinusRadiata_027973 61 768 184419 pinusRadiata_001353 421 2172 185 420 pinusRadiata_001978 163 1647186 421 pinusRadiata_002810 192 1172 187 422 pinusRadiata_002811 1311111 188 423 pinusRadiata_002812 149 1726 189 424 pinusRadiata_003514948 2228 190 425 pinusRadiata_004104 332 1465 191 426pinusRadiata_005595 232 1590 192 427 pinusRadiata_005754 207 1550 193428 pinusRadiata_006463 221 1171 194 429 pinusRadiata_006665 221 3679195 430 pinusRadiata_006750 269 1252 196 431 pinusRadiata_007030 2141242 197 432 pinusRadiata_007854 119 2065 198 433 pinusRadiata_007917186 1550 199 434 pinusRadiata_007989 244 3671 200 435pinusRadiata_008506 163 1431 201 436 pinusRadiata_008692 155 1081 202437 pinusRadiata_008693 537 1463 203 438 pinusRadiata_009170 284 1909204 439 pinusRadiata_009408 610 1659 205 440 pinusRadiata_009522 2411452 206 441 pinusRadiata_009734 223 1173 207 442 pinusRadiata_009815251 1777 208 443 pinusRadiata_010670 367 1419 209 444pinusRadiata_011297 284 1303 210 445 pinusRadiata_013098 684 1784 211446 pinusRadiata_013172 336 2738 212 447 pinusRadiata_013589 81 1622 213448 pinusRadiata_013608 399 1460 214 449 pinusRadiata_014299 207 1673215 450 pinusRadiata_014498 263 1309 216 451 pinusRadiata_014548 2322529 217 452 pinusRadiata_014610 56 2950 218 453 pinusRadiata_015460 561234 219 454 pinusRadiata_016090 193 2577 220 455 pinusRadiata_016722187 1233 221 456 pinusRadiata_016785 51 1436 222 457 pinusRadiata_017094525 2351 223 458 pinusRadiata_017527 152 1099 224 459pinusRadiata_017591 470 4114 225 460 pinusRadiata_017769 196 2007 226461 pinusRadiata_018047 214 1323 227 462 pinusRadiata_018414 68 2146 228463 pinusRadiata_018986 874 3705 229 464 pinusRadiata_019479 360 1754230 465 pinusRadiata_020144 185 1384 231 466 pinusRadiata_022480 2411533 232 467 pinusRadiata_023079 230 1435 233 468 pinusRadiata_026739101 2857 234 469 pinusRadiata_026951 43 1548 235 470 pinusRadiata_026529206 1657 710 730 pinusRadiata_000888 711 731 pinusRadiata_004578 712 732pinusRadiata_007989 713 733 pinusRadiata_009522 714 734pinusRadiata_014610 715 735 pinusRadiata_017591 716 736pinusRadiata_017769 717 737 pinusRadiata_026951

TABLE 11 Annotated Peptide Sequences of the Present Invention. EntrySequence Description Annotated Peptide Sequence 1 The amino acidsequence of SEQ ID MGDGSLGSGGRGNSGGGGGGGSRPEWLQQYDLIGKIGEG 261. Theconserved eukaryotic TYGLVFLARIKHPSTNRGKYIAIKKFKQSKDGDGVSPTA proteinkinase domain is IREIMLLREISHENVVKLVNVHINPVDMSLYLAFDYADH underlined andthe DLYEIIRHHRDKVNQAINPYTVKSLLWQLLNGLNYLHSN serine/threonine proteinkinases WIIHRDLKPSNILVMGEGEEQGVVKIADFGLARVYQAPL active-site signature isin bold. KPLSDNGVVVTIWYRAPELLLGAKHYTSAVDMWAVGCIFAELLTLKPLFQGQEVKANPNPFQLDQLDKIFKVLGHPTQEKWPMLVNLPHWQSDVQHIQRHKYDDNALGNVVRLSSKNATFDLLSKMLEYDPQKRITAAQALEHEYFRMEPLPGRNALVPSSPGDKVNYPTRPVDTTTDIEGTTSLQPSQSASSGNAVPGNMPGPHVVTNRPMPRPMHMVGMQRVPASGMAGYNLNPSGMGGGMNPSGIPMQRGVANQAQQSRRKDPGMGMGGY PPQQKQRRF 2 The amino acidsequence of SEQ ID MEKYQQLAKIGEGTYGIVYKAKDKKSGELLALKKIRLEA 262. Theconserved eukaryotic EDEGIPSTAIREISLLKQLQHPNIVRLYDVVHTEKKLTL proteinkinase domain is VFEFLDQDLKKYLDACGDNGLEPYTVKSFLYQLLQGIAF underlined andthe protein kinases CHEHRVLHRDLKPQNLLINMEGELKLADFGLARAFGIPV ATP-bindingregion and RNYTHEVVTLWYRAPDVLMGSRKYSTQVDIWSVGCIFAE serine/threonineprotein kinases MVNGRPLFPGSSEQDQLLRIFKTLGTPSLKTWPGMAELP active-sitesignatures are in DFKDNFPKYVVQSFKKICPKKLDKTGLDLLSRMLQYDPA bold.KRISAEQAMGHPYFKDLKLRKPKAAGPGP 3 The amino acid sequence of SEQ IDMDQYEKIEKIGEGTYGVVYKAIDRSTNKTIALKKIRLEQ 263. The conserved eukaryoticEDEGVPSTAIREISLLKEMQHGNIVKLQDVVHSERRLYL protein kinase domain isVFEYLDLDLKKHMDSCPEFSKDTHTIKMFLYQILRGISY underlined and the proteinkinases CHSHRVLHRDLKPQNLLLDRRTNSLKLADFGLARAFGIP ATP-binding region andVRTFTHEVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFA serine/threonine protein kinasesEMVNRRPLFPGDSEIDELFKIFRIMGTPNEDSWPGVTSL active-site signatures are inPDFKSTFPKWASQDLKTVTPTVDPAGIDLLSKMLCMDPR bold. RRITAKVALEHEYFKDVGVIP 4The amino acid sequence of SEQ IDMVMKSKLDKYEKLEKLGEGTYGVVYKAQDKTTKEIYALK 264. The conserved eukaryoticKIRLESEDEGIPSTAIREIALLKELQHPNVVRIHDVIHT protein kinase domain isNKKLILVFEFVDYDLKKFLHNFDKGIDPKIVKSLLYQLV underlined and the proteinkinases RGVAHCHQQKVLHRDLKPQNLLVSQEGILKLGDFGLARA ATP-binding region andFGIPVKNYTNEVVTLWYRAPDILLGSKNYSTSVDIWSIG serine/threonine protein kinasesCIFVEMLNQKPLFPGSSEQDQLKKIFKIMGTPDATKWPG active-site signatures are inIAELPDWKPENFEKYPGEPLNKVCPKMDPDGLDLLDKML bold.KCNPSERIAAKNAMSHPYFKDIPDNLKKLYN 5 The amino acid sequence of SEQ IDMDQYEKVEKIGEGTYGVVYKAIDRLTNETIALKKIRLEQ 265. The conserved eukaryoticEDEGVPSTAIREISLLKEMQHGNIVRLQDVVHSENRLYL protein kinase domain isVFEYLDLDLKKHMDSSPDFAKDPRLVKIFLYQILRGIAY underlined and the proteinkinases CHSHRVLHRDLKPQNLLIDRRTNALKLADFGLARAFGIP ATP-binding region andVRTFTHEVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFA serine/threonine protein kinasesEMVNQRPLFPGDSEIDELFKIFRILGTPNEDTWPGVTAL active-site signatures are inPDFKSAFPKWPAKNLQDMVPGLNSAGIDLLSKMLCLDPS bold. KRITARSALEHEYFKDIGFVP 6The amino acid sequence of SEQ IDMEKYEKLEKVGEGTYGKVYKAKDKATGQLVALKKTRLEM 266. The conserved eukaryoticDEEGVPPTALREVSLLQLLSQSLYVVRLLSVEHVDGGSK protein kinase domain isRKAAAAAAAEGGGGEAHGGGAVGGGKPMLYLVFEYLDTD underlined and the proteinkinases LKKFIDSHRKGPNPRPVPAATVQNFLYQLLKGVAHCHSH ATP-binding region andGVLHRDLKPQNLLVDKEKGILKIADLGLGRAFTVPLKSY serine/threonine protein kinasesTHEVFAFLAILLWRSEGESAADFDSXFRVSPVQVVTLWY active-site signatures are inRAPEVLLGSAHYSIGVDMWSVGCIFAEMVRRQALFPGDS bold.EFQQLLHIFRLLGTPTEKQWPGVTTLRDWHVYPQWEPQNLARAVPSLGPDGVDLLSKMLKYDPAERISAKAALDHPFF DSLDKSQF 7 The amino acidsequence of SEQ ID MERPATAAVSAMEAFEKLEKVGEGTYGKVYRAREKATGK 267. Theconserved eukaryotic IVALKKTRLHEDEEGVPPTTLREISILRMLSRDPHIVRL proteinkinase domain is MDVKQGQNKEGKTVLYLVFEYMETDLKKYIRGFRSSGES underlined andthe protein kinases IPVNIVKSLMYQLCKGVAFCHGHGVLHRDLKPHNLLMDK ATP-bindingregion and KTLTLKIADLGLARAFTVPIKKYTHEILTLWYRAPEVLL serine/threonineprotein kinases GATHYSTAVDMWSVGCIFAELVTKQALFPGDSELQQLLH active-sitesignatures are in IFRLLGTPNEKMWPGVSSLMNWHEYPQWKPQSLSTAVPN bold.LDKDGLDLLSQMLHYEPSRRISAKAAMEHPYFDDVNKTCL 8 The amino acid sequence ofSEQ ID MGCVLGREVSSGIVTESKGRDSSEVETSKRDDSVAAKVE 268. The conservedeukaryotic GEGKAEEVRTEETQKKEKVEDDQQSREQRRRSKPSTKLG protein kinase domainis NLPKHIRGEQVAAGWPSWLSDICGEALNGWIPRRANTFE underlined and theKIDKIGQGTYSNVYKAKDLLTGKIVALKKVRFDNLEPES serine/threonine protein kinasesVRFMAREILILRHLDHPNVVKLEGLVTSRMSCSLYLVFE active-site signature is inbold. YMEHDLAGLAASPAIKFTEPQVKCYMHQLLSGLEHCHNRRVLHRDIKGSNLLIDNGGVLKIGDFGLASFYDPDHKHRMTSRVVTLWYRPPELLLGANDYGVGIDLWSAGCILAELLAGKPIMPGRTEVEQLHKIYKLCGSPSEEYWKKYKLPNATLFKPREPYRRCIRETFKDFPPSSLPLIETLLAIDPAERGTATDALQSEFFRTEPYACEPSSLPQYPPSKEMDAKKRDDEARRLRAASKGQADGSKKERTRDRRVRAVPAPEANAELQHNIDRRRLISHANAKSKSEKFPPPHQDGALGFPLGASHRFDPAVVPPDVPFTSTSFTSSKEHDQTWSGPLVDPPGAPRRKKHSAGGQRESSKLSMGTNKGRRADSHLKAYESKSIA 9 The amino acid sequence of SEQID MYSKSSAVDDSRESPKDRVSSSRRLSEVKTSRLDSSRRE 269. The conserved eukaryoticNGFRARDKVGDVSVMLIDKKVNGSARFCDDQIEKKSDRL protein kinase domain isQKQRRERAEAAAAADHPGAGRVPKAVEGEQVAAGWPVWL underlined and theSAVAGEAIKGWLPRRADTFEKLDKIGQGTYSSVYKARDV serine/threonine protein kinaseTNNKIVALKRVRFDNLDTESVKFMAREIHILRMLDHPNV active-site signature is inbold. IKLEGLITSRMSCSLYLVFEYMEHDLTGLASRPDVKFSEPQIKCYMKQLLSGLDHCHKHGVLHRDIKGSNLLIDNNGILKIADFGLASVFDPHQTAPLTSRVVTLWYRPPELLLGASRYGVEVDLWSTGCILGELYTGKPILPGKTEVEQLHKIFKLCGSPSDDYWRRLHLPHAAVFKPPQPYRRCVAEIFKELPPVALGLLETLISVDPSQRGTAAFALRSEFFTASPLPCDPSSLPKYPPSKEIDMKLREEEARRRGAAGGKNELEKRGTKDSRTNSAYYPNAGQLQVKQCHSNANGRSEIFGPYQEKTVSGFLVAPPKQARVSKETRKDYAEQPDRASFSGPLVPGPGFSKAGKELGHSITVSRNTNLSTLSSLVTSRTGDNKQKSGPLVSESANQASRYSGPIREMEPARKQDRRSHVRTNIDYRSREDGNSSTKEPALYGRGSAGNKIYVSGPLLVSSNNVDQMLKEHDRRIQEHARRARFDKARVGNNHPQAAVDSKLVSV HDAG 10 The amino acid sequenceof SEQ ID MGCIPTIISDGRRRSAAPDKRRPRPRRSSSEGEAPPHAT 270. The conservedeukaryotic AAGSEGGESARGAPGKERPEPAPRFVVRSPQGWPPWLVA protein kinase domainis AVGHAIGEFVPRCADSFRKLAKIGEGTYSNVYKARDLVT underlined and theGKTVALKKVRFDNLEAESIKFMAREILVLTRLNHPNVIK serine/threonine protein kinaseLEGPVTSRMSSGLYLAFEYMEHDLSGIAARQNGKFTEPQ active-site is in boldVKCFMRQLLSGLEHCHNHDVLHRDIKCSNLLIDNEGNLKIADFGLATFYDPERKQVMTNRVVTLWYRAPELLLGATSYGIGIDLWSAGCILAELLYGKPIMPGRTEVEQLHKIFKLCGSPSEAYWNKFKLPNANIFKPPQPYARCIAETFKDFPPSALPLLETLLSIDPDERGTATTALNSEFFAAEPHACEPSSLPKYPPSKEMDLKLIKEKTRRDSSKRPSAIHGSRRDGIHDRAGRVIPAPEATAENQATLHRPRAMKKANPMSRSEKFPPAHMDGVVGSSANAWLSGPASNAAPDSRRHRSLNQNPSSSVGKASTGSSTTQETLKVAPELLQVGSSSLHPCHRMLVY GSNLTIRSK 11 The amino acidsequence of SEQ ID MGCICAKQADRGPASPGSGILTGAGTGTGTRSSKIPSGL 271. Theconserved protein kinase FEFEKSGVKEHGGRSGELRKLEEKGSLSKRLRLELGFSH familydomain is underlined, and RYVEAEQAAAGWPSWLTAVAGDAIQGLVPLKADSFEKLE theserine/threonine protein KIGQGTYSSVFRARELANGRMVALKKVRFDNFQPESIQF kinasesactive-site signature is MAREISILRRLDHPNIMKLEGIITSRMSNSIYLVFEYME in boldHDLYGLISSPQVKFSDAQVKCYMKQLLSGIEHCHQHGVIHRDVKSSNILVNNEGILRIGDFGLANILNPKDRQQLTSHVVTLWYRPPELLMGSTSYGVTVDLWSVGCVFAELMFRKPILRGRTEVEQLHKIFKLCGSPPDGYWKMCKVPQATMFRPRHAYECTLRERCKGIATSAMKLMETFLSIEPHKRGTASSALISEYFRTVPYACDPSSLPKYPPNKEIDAKHREEARRKKARSRVREAEVGKRPTRIHRASQEQGFSSNIAPKEKRSYA 12 The amino acid sequence ofSEQ ID MAVAAPGHLNVNESPSWGSRSVDCFEKLEQIGEGTYGQV 272. The conservedeukaryotic YMAKEKKTGEIVALKKIRMDNEREGFPITAIREIKILKK protein kinase domainis LHHENVIKLKEIVTSPGPEKDEQGRPEGNKYKGGIYMVF underlined and the proteinkinases EYMDHDLTGLADRPGMRFSVPQIKCYMRQLLTGLHYCHI ATP-binding region andNQVLHRDIKGSNLLIDNEGNLKLADFGLARSFSNDHNAN serine/threonine protein kinasesLTNRVITLWYRPPELLLGATKYGPAVDMWSVGCIFAELL active-site signatures are inHGKPIFPGKDEPEQLNKIFELCGAPDEINWPGVSKIPWY bold.NNFKPTRPMKRRLREVFRHFDRHALELLERMLTLDPSQRISAKDALDAEYFWADPLPCDPKSLPKYESSHEFQTKKKRQQQRQHEETAKRQKLQHPPQHPRLPPVQQSGQAHAQMRPGPNQLMHGSQPPVATGPPGHHYGKPRGPSGGAGRYPSSGNPGGGYNHPSRGGQGGSGGYNSGPYPPQGRAPPYGSSGMPGAGPRGGGGNNYGVGPSNYPQGGGGPYGGSGAGRGSNM MGGNRNQQYGWQQ 13 The amino acidsequence of SEQ ID MGCICTKGILPAHYRIKDGGLKLSKSSKRSVGSLRRDEL 273. Theconserved AVSANGGGNDAADRLISSPHEVENEVEDRKNVDFNEKLS serine/threonineprotein kinase KSLQRRATMDVASGGHTQAQLKVGKVGGFPLGERGAQVV domain isunderlined, and the AGWPSWLTAVAGEAINGWVPRRADSFEKLEKIGQGTYSSserine/threonine protein kinase VYRARDLETNTIVALKKVRFANMDPESVRFMAREIIIMRactive-site signature is in bold.KLDHPNVMKLEGLITSRVSGSLYLVFEYMDHDLAGLAATPSIKLTESQIKCYMQQLLRGLEYCHSHGVLHRDIKGSNLLVDNNGNLKIGDFGLATFFRTNQKQPLTSRVVTLWYRPPELLLGSSDYGASVDLWSSGCILAELFAGKPIMPGRTEVEQLHKIFKLCGSPSEEYWKKSKLPHATIFKPQQPYKRCLLETFKDFPSSALGLLDVLLAVEPECRGTASSALQNEFFTSNPLPSDPSSLPKYPSSKEFDARLRDEEARKHKATAGKARGLESIRKGSKESKVVPTSNANADLKASIQKRQEQSNPRSTGEKPGGTTQNNFILSGQSAKPSLNGSTQIGNANEVEALIVPDRELDSPRGGAELRRQRSFMQRRASQLSRFSNSVAVGGDSHLDCSREKGANTQWRDEGFVARCSHPDGGELAGKHDWSHHLLHRPISLFKKGGEHSRRDSIASYSPKKGRIHYSGPLLPSGDNLDEMLKEHERQIQNAVRKARLDKVKTKREY ADHGQTESLLCWANGR 14 The aminoacid sequence of SEQ ID MDPDPSPDPDPPKSWSIHTRREIIARYEILERVGSGAYS 274. Theconserved protein kinase DVYRGRRLSDGLAVALKEVHDYQSAFREIEALQILRGSP familydomain is underlined and HVVLLHEYFWREDEDAVLVLEFLRSDLAAVIADASRRPR theserine/threonine protein DGGGGGAAALRAGEVKRWMLQVLEGVDACHRNSIVHRDL kinasesactive-site signature is KPGNLLISEEGVLKIADFGQARILLDDGNVAPDYEPESF inbold. EERSSEQADILQQPETMEADTTCPEGQEQGAITREAYLREVDEFKAKNPRHEIDKETSIFDGDTSCLATCTTSDIGEDPFKGSYVYGAEEAGEDAQGCLTSCVGTRWFRAPELLYGSTDYGLEVDLWSLGCIFAELLTLEPLFPGISDIDQLSRIFNVLGNLSEEVWPGCTKLPDYRTISFCKIENPIGLESCLPNCSSDEVSLVRRLLCYDPAARATPMELLQDKYFTEEPLPVPISALQVPQSKNSHDEDSAGGWYDYNDMDSDSDFEDFG PLKFTPTSTGFSIQFP 15 The aminoacid sequence of SEQ ID MDPDPSPSPDPPKSWSIHTRREIIARYEILERVGSGAYS 275. Theconserved DVYRGRRLSDGLAVALKEVHDYQSAFREIEALQILRGSP serine/threonineprotein kinase HVVLLHEYFWREDEDAVLVLEFLRSDLAAVIADASRRPR domain isunderlined, and the GGGVAPLRAGEGKRWMLQVLEGVDACHRNSIVHRDLKPGserine/threonine protein kinase NLLISEEGVLKIADFGQARILLDDGNVAPDYEPESFEERactive-site signature is in bold.SSEQADILQQPETMEADTTCPEGQEQGAITREAYLREVDEFKAKNPRHEIDKETSIYDGDTSCLATCTTSDIGEDPFKGSYVYGAEEAGEDAQGSLTSCVGTRWFRAPELLYGSTDYGLEVDLWSLGCIFAELLTLEPLFPGISDIDQLSRIFNVLGNLSEEVWPGCTKLPDYRTISFCKIENPIGLESCLPNCSSDEVSLVRRLLCYDPAARATPMELLQDKYFTEEPLPVPISALQVPQSKNSHDEDSAGGWYDYNDMDSDSDFEDFGPLK FTPTSTGFSIQFP 16 The amino acidsequence of SEQ ID MSNQHRRSSFSSSTTSSLAKRHASSSSSSLENAGKAFAA 276. Theconserved cyclin and AAVPSHLAKKRAPLGNLTNLKAGDGNSRSSSAPSTLVAN cyclinC-terminal domains are ATKLAKTRKGSSTSSSIMGLSGSALPRYASTKPSGVLPSunderlined and the cyclins VNPSIPRIEIAVDPMSCSMVVSPSRSDMQSVSLDESMSTsignature is in bold. CESFKSPDVEYIDNEDVSAVDSIDRKTFSNLYISDAAAKTAVNICERDVLMEMETDEKIVNVDDNYSDPQLCATIACDIYQHLRASEAKKRPSTDFMDRVQKDITASMRAILIDWLVEVAEEYRLVPDTLYLTVNYIDRYLSGNVMNRQRLQLLGVACMMIAAKYEEICAPQVEEFCYITDNTYFKEEVLQMESSVLNYLKFEMTAPTVKCFLRRFVRAAQGVNEVPSLQLECMANYIAELSLLEYDMLCYAPSLVAASAIFLAKFVITPSKRPWDPTLQHYTLYQPSDLGNCVKDLHRLCFNNHGSTLPAI REKYSQHKYKYVAKKYCPPSIPPEFFHNLVY17 The amino acid sequence of SEQ IDMNKENAVGTKSEAPTIRITRSRSKALGTSTGMLPSSRPS 277. The conserved cyclin andFKQEQKRTVRANAKRSASDENKGTMVGNASKQHKKRTVL cyclin C-terminal domains areNDVTNIFCENSYSNCLNAAKAQTSRQGRKWSMKKDRDVH underlined.QSGAVQIMQEDVQAQFVEESSKIKVAESMEITIPDKWAKRENSEHSISMKDTVAESSRKPQEFICGEKSAALVQPSIVDIDSKLEDPQACTPYALDIYNYKRSTELERRPSTIYMETLQKDVTPNMRGILVDWLVEVSEEYKLVPDTLYLTVNLIDRSLSQKFIEKQRLQLLGVTCMLIASKYEEICPPRVEEFCFITDNTYTSLEVLKMESRVLNLLHFQLSVPTVKTFLRRFVQAAQVSSEVPSVELEYLANYLAELTLVEYSFLKFLPSLMAASAVLLARWTLNQSDNPWNLTLEHYTKYKASELKAAVLALEDLQLNTSGSTLNAIREKYRQQKVNYSLLIHSKANH EIL 18 The amino acid sequenceof SEQ ID MAGSDENNPGVVGGAHVQEGLRVGAGKMGAGNVQQRRAL 278. The conservedcyclin N- and SNINSNIIGAPPYPCAVNKRVLSEKNVNSENDLLNAAHR C-terminal familydomains are PITRQFAAQMAYKQQLRPEENKRTTQSVSNPSKSEDCAI underlined and thecyclins LDVDDDKMADDFPVPMFVQHTEAMLEEIDRMEEVEMEDV signature is in bold.AEEPVTDIDSGDKENQLAVVEYIDDLYMFYQKAEASSCVPPNYMDRQQDINERMRGILIDWLIEVHYKFELMDETLYLTVNLIDRFLAVQPVVKKKLQLVGVTAMLLACKYEEVSVPVVEDLILISDRAYSRKEVLEMERLMVNTLHFNMSVPTPYVFMRRFLKAAQSDKKLELLSFFIIELSLVEYDMLKFPPSLLAASAIYTALSTITRTKQWSTTCEWHTSYSEEQLLECARLMVTFHQRAGSGKLTGVHRKYSTSKFGHAARTEPANFL LDFRL 19 The amino acid sequenceof SEQ ID MASRPIVPVQARGEAAIGGGAGKAAIGGGAGKQQKKNGA 279. The conservedcyclin and AEGRNRKALGDIGNLVTVRGIEGKVQPHRPITRSFCAQL cyclin C-terminaldomains are LANAQAAAAAENNKKQAVVNVNGAPSILDVPGAGKRAEP underlined.AAAAAAAVAKAAQKKVVKPKQKAEVIDLTSDSEERSRPRRSNNIMSLRRRKERNHREGICPLSLRSSLLEARLVDWLIEIHNKFDLMPETLYLTINIIDRFLSVKAVPRRELQLLGMGALFTASKYEEIWAPEVNDLVCIADRAYSHEQVLAMEKTILGKLEWTLTVPTHYVFLVRFIKASLGDRKLENMVYFLAELGVMNYATLTYCPSMVAASAVYAARCTLGLTPLWNDTLKLHTGFSESQLMDCARLLVGYHAKAKENKLQVVYKKYSS SQREGVALIPPAKALLCEGGGLSSSSSLASSS20 The amino acid sequence of SEQ IDMGLPDENNAALSKPTNLQVGGLEIGGRKFGQEIRQTRRA 280. The conserved cyclin andLSVINQNLVGDRAYPCHVVNKRGHSKRDAVCGKDQVDPV cyclin C-terminal domains areHRPLTRKFAAQTASTQQHCIEEAKKPRTAVQERNEFGDC underlined and the cyclinsIFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMED signature is in bold.IVEEEEEEPIMDIDGRDKKNPLAVVDYIEDIYANYRRTENCSCVSANYMAQQADINEKMRSILIDWLIEVHDKFDLMHETLFLTVNLIDRFLARQSVVRKKLQLVGLVAMLLACKYEEVSVPVVGDLILISDKAYTRKEVLEMESLMLNSLQFNMSVPTPYVFMRRFLKAAESDKKLEVLSFFLIELSLVEYEMVKFPPSLLAAAAIFTAQCTLYGFKQWTKTCEWHSNYTEDQLLECARMMVGFHQKAATGKLTGVHRKYGTSKFGYTSKCE PANFLLGEMKNP 21 The amino acidsequence of SEQ ID MGLPDENNAALSKPTNLQVGGLEIGGRKFGQEIRQTRRA 281. Theconserved cyclin and LSVINQNLVGDRAYPCHVVNKRGHSKRDAVCGKDQVDPV cyclinC-terminal domains are HRPLTRKFAAQTASTQQHCIEEAKKPRTAVQERNEFGDCunderlined and the cyclins IFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMEDsignature is in bold. IVEEEEEEPIMDIDGRDKKNPLAVVDYIEDIYANYRRTENCSCVSANYMAQQADINEKMRSILIDWLIEVHDKFDLMHETLFLTVNLIDRFLARQSVVRKKLQLVGLVAMLLACKYEEVSVPVVGDLILISDKAYTRKEVLEMEKLMLNSLQFNMSVPTPYVFMRRFLKAAESDKKLEVLSFFLIELSLVEYEMVKFPPSLLAAAAIFTAQCTLYGFKQWTKTCEWHSNYTEDQLLECARMMVGFHQKAATGKLTGVHRKYGTSKFGYTSKCE AANFLLGEMKNP 22 The amino acidsequence of SEQ ID MAMVQRQGHDPSSPQEQEDGPSSFLSDDALYCEEGRFEE 282. Theconserved cyclin N- and DDGGGGGQVDGIPLFPSQPADRQQDSPWADEDGEEKEEEC-terminal family domains are EAELQSLFSKERGARPELAKDDGGAVAARREAVEWMLMVunderlined. RGVYGFSALTAVLAVDYLDRFLAGFRLQRDNRPWMTQLVAVACLALAAKVEETDVPLLVELQEVGDARYVFEAKTVQRMELLVLSTLGWEMHPVTPLSFVHHVARRLGASPHHGEFTHWAFLRRCERLLVAAVSDARSLKHLPSVLAAAAMLRVIEEVEPFRSSEYKAQLLSALHMSQEMVEDCCRFILGIAETAGDAVTSSLDSFLKRKRRCGHLSPRSPSGVIDASFSCDDESNDSWATDPPSDPDDNDDLNPLPKKSRSSSPSSSPSSVP DKVLDLPFMNRIFEGIVNGSPI 23 Theamino acid sequence of SEQ ID MEASYQPHHHGHLRQHDPSSSQQEEQVPFDALYCSEEHW283. The conserved cyclin and GEEDEEEGLASDGLLSEERDHRLLSPRALLDQDLLWEDEcyclin C-terminal domains are ELASLFSKEEPGGMRLNLENDPSLADARREAVEWIMRVHunderlined. AHYAFSALTALLAVNYWDRFTCSFALQEDKPWMTQLSAVACLSLAAKVEETQVPLLIDFQVEDSSPVFEAKNIQRMELLVLSSLEWKMNPVTPLSFLDYMTRRLGLTGHLCWEFLRRCENVLLSVISDCRFTCYLPSVIAASTMLHVINGLKPRLDVEDQTQLLGILAMGMDKIDACYKLIDDDHALRSQRYSHNKRKFGSVPGSPRGVMELCFSSDGSNDSWSVAASVSSSPEPHSKKSRAGEEAEDRLLRGLEGEEDDPASADIFSFPH 24 The amino acid sequence of SEQID MALQEEDTRRHYPTAPPFSPDGLYCEDETFGEDLADNAC 284. The conserved cyclin andEYAGGGARDGLCEIKDPTLPPSLLGQDLFWEDGELASLV cyclin C-terminal domains areSRETGTHPCWDELISDGSVALARKDAVGWILRVHGHYGF underlined.RPLTAMLAVNYLDRFFLSRSYQRDRPWISQLVAVACLSVAAKVEETQVPILLDLQVANAKFVFESRTIQRMELLLMSTLDWRMNSVTPISFFDHILRRFGLTTNLHRQFFWMCERLLLSVVADVRLASFLPSVVATAAMLYVNKEIEPCICSEFLDQLLSLLKINEDRVNECYELILELSIDHPEILNYKHKRKRGSVPSSPSGVIDTSFSCDSSNDSWGVASSVSSSLEPRFK RSRFQDQQMGLPSVNVSSMGVLNSSY 25The amino acid sequence of SEQ IDMGQIQYSEKYFDDTYEYRHVVLPPDVAKLLPKNRLLSEN 285. The conserved cyclin-EWRAIGVQQSRGWVHYAIHRPEPHIMLFRRPLNYQQQQE dependent kinases regulatoryNQAQQNMLAK subunit domain is underlined and the cyclin-dependent kinasesregulatory subunits signature 1 is in bold. 26 The amino acid sequenceof SEQ ID MGSIDPPKAEQNGTAAAAVADPGQKPGAGDAMPPPPPVK 286. The conservedchromo domain HSNGTAAEPDVATKRRRMSVLPLEVGTRVMCRWRDGKYH is underlined andthe MOZ/SAS-like PVKVIERRKLNPGDPNDYEYYVHYTEFNRRLDEWVKLEQ protein domainis in bold/italics. LDLNSVETVVDEKVEDKVTGLKMTRHQKRKIDETHVEGHEELDAASLREHEEFTKVKNIATIELGRYEIETWYFSPFPPEYNDCSKLYFCEFCLNFMKRKEQLQRHMKKCD

PKVLDRHLKAAGRG GLEVDVSKLIWTPYREQG 27 The amino acid sequence of SEQ IDMDTGGNSLPSGPDGVKRKVCYFYDPEVGNYYLLQHMQVL 292. The conserved histoneKPVPARDRDLCRFHADDYVAFLRSITPETQQDQLRQLKR deacetylase family domain isFNVGEDCPVFDGLHSFCQTYAGGSVGGAVKLNHGLCDIA underlined.INWAGGLHHAKKCEASGFCYVNDIVLGILELLKQHERVLYVDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGDIRDIGYGKGKYYSLNVPLDDGIDDESYHSLFKPIIGKVMEVFKPGAVVLQCGADSLSGDRLGCFNLSIKGHAECVRYMRSFNVPVLLLGGGGYTIRNVARCWCYETGVALGLEVDDKMPQHEYYEYFGPDYTLHVAPSNMENKNSRQLLEEIRSKLLENLSKLQHAPSVPFQERPPDTELPEADEDQEDPDERWDPDSDMDVDEDRKPLPSRVKRELIVEPEVKDQDSQKASIDHGRGLDTTQEDNASIKVSDMNSMITDEQSVKMEQDNVNK PSEQIFPK 28 The amino acidsequence of SEQ ID MDTGGNSLPSGPDGVKRKVCYFYDPEVGNYYYGQGHPMK 293. Theconserved histone PHRIRMTHALLAHYGLLQHMQVLKPVPARDRDLCRFHAD deacetylasefamily domain is DYVAFLRSITPETQQDQLRQLKRFNVGEDCPVFDGLHSF underlined.CQTYAGGSVGGAVKLNHGLCDIAINWAGGLHHAKKCEASGFCYVNDIVLGILELLKQHERVLYVDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGDIRDIGYGKGKYYSLNVPLDDGIDDESYHSLFKPIIGKVMEVFKPGAVVLQCGADSLSGDRLGCFNLSIKGHAECVRYMRSFNVPVLLLGGGGYTIRNVARCWCYETGVALGLEVDDKMPQHEYYEYFGPDYTLHVAPSNMENKNSRQLLEDIRSKLLENLSKLQHAPSVPFQERPPDTELPEADEDQEDPDERWDPDSDMDVDEDRKPLPSRVKRELIVEPEVKDQDSQKASIDHGRGLDTTQEDNASIK VSDMNSMITDEQSVKMEQDNVNKPSEQIFPK29 The amino acid sequence of SEQ IDMRPKDRISYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVL 294. The conserved histoneSYELHTKMEIYRPHKAYPAELAQFHSPDYVEFLHRITPD deacetylase domain isunderlined. TQHLFPNDLAKYNLGEDCPVFENLFEFCQIYAGGTIDAARRLNNQLCDIAINWAGGLHHAKKCEASGFCYINDLVLGILELLKYHARVLYIDIDVHHGDGVEEAFYFTDRVMTVSFHKFGDMFFPGTGDVKEIGGKEGKFYAINVPLKDGIDDTSFTRLFKAIISKVVETYQPGAIVLQCGADSLAGDRLGCFNLSIDGHSECVRFVKKFNLPLLVTGGGGYTKENVARCWVVETGVLLDTELPNEIPENEYFKYFAPDYSLKIPRGNIVLENLNSKSYLSAIKVQVLENLRNIQHAPSVQMQEVPPDFYIPDFDEDEQNPDERMDQHTQDKQIQRDDEYYDGDNDNDHNM DD 30 The amino acid sequence ofSEQ ID MTVAEDFHVNNRSKMVSQATPESRLTGGEDDNSLHNQVD 295. The conservedhistone ELLCQELPERQVILEFEGTRPKPYFSDHNGGENSALGVR deacetylase familydomain is ATEDDLNSDVEAEEKQKEMTLEDMYKNDGTLYDDDEDDS underlined and theZinc finger DWEPVKRQVELMRWFCTNCTMVNVEDVFLCDICGEHRDS RanBP2-type profileis in bold. GILRHGFYASPFMQDVGAPSVEAEVQESREDHARSSPPSSSTVVGFDEKMLLHSEVEMKSHPHPERADRLQAIAASLATAGIFPGRCRSLPVREITKEELQMVHSSEHVDAVEMTSHMFSSYFTPDTYANEHSARAARIAAGLCADLASTIISGRSKNGFALVRPPGHHAGIKHAMGFCLHNNAAVAALAAQGAGAKKVLIVDWDVHHGNGTQEIFDGNKSVLYISLHRHEGGNFYPGTGAAHEVGTMGAEGYCVNIPWSRRGVGDNDYVFAFHHIVLPIASAFAPDFTIISAGFDAARGDPLGCCDVTPAGYAQMTHMLSALSGGKLLVILEGGYNLRSISSSAVAVIKVLLGDSPISEIADAVPSKAGLRTVLEVLKIQRSYWPSLESIFWELQSQWGMFLVDNRRKQIRKRRRVLVPIWWKWGRKS VLYHLLNGHLHVKTKR 31 The aminoacid sequence of SEQ ID MAAAPSSPPTNRVDVFWHDGMLSHDTGRGVFDTGSDPGF 296. Theconserved histone LDVLEKHPENPDRVRNMVSILKRGPISPFISWHTATPAL deacetylasefamily domain is ISQLLSFHSPEYINELVEADKNGGKVLCAGTFLNPGSWD underlined.AALLAAGNTLSAMKYVLDGKGKIAYALVRPPGHHAQPSQADGYCFLNNAGLAVRLALDSGCKRVVVVDIDVHYGNGTAEGFYQSSDVLTISLHMNHGSWGPSHPQSGSVDELGEDEGYGYNMNIPLPNGTGDRGYEYAVTELVVPAVESFKPEMVVLVVGQDSSAFDPNGRQCLTMDGYRAIGRTIRGLADRHSGGRILIVQEGGYHVTYSAYCLHATVEGILDLPDPLLADPI AYYPEDEAFPVKVVDSIKRYLVDKVPFLKEH32 The amino acid sequence of SEQ IDMVESSGGASLPSVGQDARKRRVSYFYEPTIGDYYYGQGH 297. The conserved histonePMKPHRIRMAHNLIVHYYLHRRMEISRPFPAATTDIRRF deacetylase family domain isHSEDYVTFISSVTPETVSDPAFSRQLKRFNVGEDCPVFD underlined.GIFGFCQASAGGSMGAAVKLNRGDSDIALNWAGGLHHAKKSEASGFCYVNDIVLGILELLKVHKRVLYVDIDVHHGDGVEEAFYTTDRVMTVSFHKFGDFFPGSGHIKDTGAGPGKNYALNVPLNDGIDDESFRGMFRPIIQKVMEVYQPDAVVLQCGADSLSGDRLGCFNLSVKGHADCLRFLRSFNVPLMVLGGGGYTMRNVARCWCYETAVAVGVEPENDLPYNEYYEYFGPDYTLHVEPCSMENLNAPKDLERIRNMLLEQLSRIPHAPSVPFQMTPPITQEPEEAEEDMDERPKPRIWNGEDYESDAEEDKSQHRSSNADALHDENVEMRDSVGENSGDKTREDRS PS 33 The amino acid sequence ofSEQ ID MAAIISCHHYHSCCSSLIASKWVGARIPTSCFGRSSTQS 299. The conservedcyclophilin- NNAASVRQFVTRCSSSPSSRGQWQPHQNGEKGRSFSLRE typepeptidyl-prolyl cis-trans CAISIALAVGLVTGVPSLDMSTGNAYAASPALPDLSVLIisomerase family domain is SGPPIKDPEALLRYALPINNKAIREVQKPLEDITDSLKVunderlined. AGLRALDSVERNVRQASRVLKQGKNLIVSGLAESKKDHGVELLDKLEAGMDELQQIVEDGNRDAVAGKQRELLNYVGGVEEDMVDGFPYEVPEEYKNMPLLKGRAAVDMKVKVKDNPNLEECVFRIVLDGYNAPVTAGNFVDLVERHFYDGMEIQRADGFVVQTGDPEGPAESFIDPSTEKPRTIPLEIMVDGEKAPVYGATLEELGLYKAQTKLPFNAFGTMAMARDEFEDNSASSQIFWLLKESELTPSNANILDGRYAVFGYVTENQDFL ADLKVGDVIESVQVVSGLDNLANPSYKIAG34 The amino acid sequence of SEQ IDMAGEDFDIPPADEMNEDFDLPDDDDDAPVMKAGDEKEIG 300. The conserved FKBP-typeKQGLKKKLVKEGDAWETPDNGDEVEVHYTGTLLDGTQFD peptidylprolyl isomerase domainsSSRDRGTPFKFTLGQGQ

are underlined. The FKBP-type

EAGSPPTIPPNATLQFDVELLSWTSVKDICKD peptidyl-prolyl cis-transGGIFKKILVEGEKWENPKDLDEVLVKYEFQLEDGTTIAR isomerase signature 1 is in boldSDGVEFTVKEGHFCPAVAKAVKTMKKGEKVLLTVKPQYG and the FKBP-typepeptidyl-prolyl FGEKGKPASGDEGAVPPNATLQITLELVSWKTVSEVTDD cis-transisomerase signature 2 is KKVIKKILKEGEGYERPNEGAVVEVKLIGKLQDGTVFVK inbold/italics. KGHDDCEELFKFKIDEEQ

SSESKQDLAVVPPSSTVYYEVELVSFVKDKE SWDMNTEEKIEAAGKKKEEGNVIFKAGKYAKASKRYEKAVKYIEYDTSFSEDEKKQAKALKVACNLNDAACKLKLKDYNQAEKLCTKVLELDSRNVKALYRRAQAYIELSDLDLAEFDIKKALEIDPHNRDVKLEYKVLKEKVKEFNKKDAKFYGN MFAKMSKLEPVEKTAAKEPEPMSIDSKA 35The amino acid sequence of SEQ IDMSTVYVLEPPTKGKVVLNTTHGPLDVELWPKEAPKAVRN 301. The conserved cyclophilin-FVQLCLEGYYDNTIFHRIIKDFLVQGGDPTGSGTGGESI type peptidyl-prolyl cis-transYGDAFSDEFHSRLRFKHRGLVACANAGSPHSNGSQFFIT isomerase family domain isLDRCDWLDRKNTIFGKITGDSIYNLSGLAEVETDKSDRP underlined and the cyclophilin-LDPPPKIISVEVLWNPFEDIVPRAPVRSLVPTVPDVQNK type peptidyl-prolyl cis-transEPKKKAVKKLNLLSFGEEAEEEEKALVVVKQKIKSSHDV isomerase signature is in bold.LDDPRLLKEHIPSKQVDSYDSKTARDVQSVREALSSKKQELQKESGAEFSNSFREIADDEDDDDDDASFDARMRRQILQKRKELGDLPPKPKPKSRDGISARKERETSISRDKDDDDDDDQPRVEKLSLKKKGIGSEARGERMANADADLQLLNDAERGRQLQKQKKHRLRGREDEVLTKLETFKASVFGKPLASSAKVGDGDGDLSDWRSVKLKFAPEPGKDRMTRNEDPNDYVVVDPLLEKGKEKFNRMQAKEKRRGREWAGKSLT 36 The amino acid sequence of SEQ IDMASAISMHSSGLLLLQGTNGKDVTEMGKAPASSRVANMQ 302. The conserved cyclophilin-QRKYGATCCVARGLTSRSHYASSLAFKQFSKTPSIKYDR type peptidyl-prolyl cis-transMVEIKAMATDLGLQAKVTNKCFFDVEIGGEPAGRIVIGL isomerase family domain isFGDDVPKTVENFRALCTGEKGFGYKGCSFHRIIKDFMIQ underlined and the cyclophilin-GGDFTRGNGTGGKSIYGSTFEDENFALKHVGPGVLSMAN type peptidyl-prolyl cis-transAGPSTNGSQFFICTVKTPWLDNRHVVFGQVVDGMDVVQK isomerase signature is in bold.LESQETSRSDVPRQPCRIVNCGELPLDG 37 The amino acid sequence of SEQ IDMAASFTALSNVGSLSSPRNGSEIRRFRPSCNVAASVRPP 303. The conserved cyclophilin-PLKAGLSASSSSSFSGSLRLIPLSSSPQRKSRPCSVRAS type peptidyl-prolyl cis-transAEAAAAQSKVTNKVYLDISIGNPVGKLVGRIVIGLYGDD isomerase signature isunderlined. VPQTAENFRALCTGEKGFGYKGSTVHRVIKDFMIQGGDFDKGNGTGGKSIYGRTFKDENFKLSHVGPGVVSMANAGPNTNGSQFFICTVKTPWLDQRHVVFGQVLEGMDIVRLIESQ ETDRGDRPRKRVVVSDCGELPVV 38 Theamino acid sequence of SEQ ID MAEAIDLTGDGGVMKTIVRRAKPDAVSPSETLPLVDVRY304. The conserved FKBP-type EGVLAETGEVFDSTHEDNTLFSFEIGKGSVISAWDTALRpeptidyl-prolyl cis-trans TMKVGEVAKITCKPEYAYGSTGSPPDIPPDATLIFEVELisomerase signature is underlinedVACKPCKGFSVTSVTEDKARLEELKKQREIAAATKEEEK and the FKBP-typepeptidyl-prolyl KRREEAKAAAAARVQAKLDAKKGHGKGKGKAK cis-trans isomerasesignature 2 is in bold. 39 The amino acid sequence of SEQ IDMGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRAL 305. The conserved cyclophilin-CTGEKGAGRSGKPLHYKGSSFHRVIPGFMCQGGDFTAGN type peptidyl-prolyl cis-transGTGGESIYGSKFADENFVKKHTGPGVLSMANAGPGTNGS isomerase family domain is1QFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSS underlined and the cyclophilin-GRTSKPVVVADCGQLS type peptidyl-prolyl cis-trans isomerase signature isin bold. 40 The amino acid sequence of SEQ IDMPNPKVFFDMTIGGAAAGRVVMELYADTTPRTAENFRAL 306. The conserved cyclophilin-CTGEKGVGRSKKPLHYKGSKFHRVIPSFMCQGGDFTAGN type peptidyl-prolyl cis-transGTGGESIYGVKFADENFIKKHTGPGILSMANAGPGTNGS isomerase signature isunderlined QFFICTTKTEWLDGKHVVFGKVVEGMEVVKAIEKVGSSS and thecyclophilin-type peptidyl- GRTSKPVVVADCGQLP prolyl cis-trans isomerasesignature is in bold. 41 The amino acid sequence of SEQ IDMAEAIDLTGDGGVMKTIVRRAKPDAVSPSETLPLVDVRY 307. The conserved FKBP-typeEGVLAETGEVFDSTHEDNTLFSFEIGKGSVISAWDTALR peptidyl-prolyl cis-transTMKVGEVAKITCKPEYAYGSTGSPPDIPPDATLIFEVEL isomerase signature isunderlined VACKPCKGFSVTSVTEDKARLEELKKQREIAAATKEEEK and the FKBP-typepeptidyl-prolyl KRREEAKAAAAARVQAKLDAKKGHGKGKGKAK cis-trans isomerasesignature 2 is in bold. 42 The amino acid sequence of SEQ IDMATARSFFLCALLLLATLYLAQAKKSEDLKEVTHKVYFD 308. The conserved cyclophilin-VEIAGKPAGRIVMGLYGKAVPKTAENFRALCTGEKGTGK type peptidyl-prolyl cis-transSGKPLHYKGSSFHRIIPSFMLQGGDFTLGDGRGGESIYG isomerase signature isunderlined EKFADENFKLKHTGPGLLSMANAGPDTNGSQFFITTVTT and thecyclophilin-type peptidyl- SWLDGRHVVFGKVLSGMDVVYKVEAEGRQSGTPKSKVVIprolyl cis-trans isomerase ADSGELPL signature is in bold. 43 The aminoacid sequence of SEQ ID MMRREISVLLQPRFVLAFLALAVLLLVFAFPFSRQRGDQ 309. Theconserved cyclophilin- VEEEPEITHRVYLDVDIDGQHLGRIVIGLYGEVVPRTVE typepeptidyl-prolyl cis-trans NFRALCTGEKGKSANGKKLHYKGTPFHRIISGFMIQGGDisomerase family domain is VIYGDGKGYESIYGGTFADENFRIKHSHAGIISMVNSGPunderlined and the cyclophilin- DSNGSQFFITTVKASWLDGEHVVFGRVIQGMDTVYAIEGtype peptidyl-prolyl cis-trans GAGTYNGKPRKKVIIADSGEIPKSKWDEER isomerasesignature is in bold. 44 The amino acid sequence of SEQ IDMWATAEGGPPEVTLETSMGSFTVELYFKHAPRTSRNFIE 310. The conserved cyclophilin-LSRRGYYDNVKFHRIIKDFIVQGGDPTGTGRGGESIYGK type peptidyl-prolyl cis-transKFEDEIKPELKHTGAGILSMANAGPNTNGSQFFITLAPC isomerase family domain isPSLDGKHTIFGRVCRGMEIIKRLGSVQTDNNDRPIHDVK underlined and the cyclophilin-ILRTSVKD type peptidyl-prolyl cis-trans isomerase signature is in bold.45 The amino acid sequence of SEQ IDMSNPKVFFDILIGKMKAGRVVMELFADVTPKTAENFRAL 311. The conserved cyclophilin-CTGEKGIGRSGKPLHYKGSTFHRIIPNFMCQGGDFTRGN type peptidyl-prolyl cis-transGTGGESIYGMKFADENFKIKHTGLGVLSMANAGPDTNGS isomerase family domain isQFFICTEKTPWLDGKHVVFGKVIDGYNVVKEMESVGSDS underlined and the cyclophilin-GSTRETVAIEDCGQLSEN type peptidyl-prolyl cis-trans isomerase signature isin bold. 46 The amino acid sequence of SEQ IDMDDDFEFPASSNVENDDDDGMDMDDMGGDVPEEEDPVAS 312. The conserved FKBP-typePAVLKVGEEREIGKAGFKKKLVKEGEGWETPSSGDEVEV peptidylprolyl isomerase domainsHYTGTLLDGTKFDSSRDRGTPFKFKLGRGQ

are underlined. The FKBP-type

ESGSPPTIPPNATLQFDVE peptidyl-prolyl cis-transLLSWSSVKDICKDGGILKKVLVEGEKWDNPKDLDEVFVK isomerase signature 1 is in boldYEASLEDGTLISKSDGVEFTVGDGYFCAALAKAVKTMKK and the FKBP-typepeptidyl-prolyl GEKVLLTVMPQYAFGETGRPASGDEAAVPPDASLQIMLE cis-transisomerase signature 2 is LVSWKTVSDVTKDKKVLKKTLKEGEGYERPNDGAAVQVR inbold/italics. The TPR repeat LCGKLQDGTVFVKKDDEEPFEFKIDEEQ

is in italics.

PTESQQDLAVVPANSTVYYEV ELLSFVKEKESWEMNNQEKIEAAARKKEEGNAAFKAGKYVRASKRYEKAVRFIEYDSSFSDEEKQQAKTLKNTCNLNDAACKLKLKDFKEAEKLCTKVLEGDGKNVKALYRRAQAYIQLVDLDLAEQDIKKALEIDPNNRDVKLEYKILKEKVREYNKRDAQFYGNMFAKMNKLEHSRTAGMGAKHEAAPMTIDS KA 47 The amino acid sequence ofSEQ ID MAKPRCFMDISIGGELEGRIVGELYTDVAPKTAENFRAL 313. The conservedcyclophilin- CTGEKGIGPHTGAPLHYKGVRFHRVIKGFMVQGGDISAG typepeptidyl-prolyl cis-trans DGTGGESIYGLKFEDENFDLKHERKGMLSMANSGPNTNGisomerase family domain is SQFFITTTRTSHLDGKHVVFGRVVKGMGVVRSVEHVTTAunderlined and the cyclophilin- AGDCPTVDVVIADCGEIPAGADDGIRNFFKDGDTYPDWPtype peptidyl-prolyl cis-trans ADLDESPAELSWWMDAVDSIKAFGNGSYKKQDYKMALRKisomerase signature is in bold. YRKALRYLDICWEKEGIDEVESSSLRKTKSQIFTNSSACThe TPR repeat is in bold/italics. KLKLCDLKGALLDAEFAVRDGENN

GIKKELNAAKKKIFERREQ EKRAYRKMFL 48 The amino acid sequence of SEQ IDMTKRKNPLVFLDVSIDGDPVERIVIELFADTVPRTAENF 314. The conserved cyclophilin-RSLCTGEKGVGKTTGKPLHYKGSYFHRIIKGFMAQGGDF type peptidyl-prolyl cis-transSNGNGTGGESIYGGKFADENFKLAHDGPGLLSMANGGPN isomerase signature isunderlined TNGSQFFIIFKRQPHLDGKHVVFGKVMRGMEVVKKIEQV and thecyclophilin-type peptidyl- GSANGKPLQPVKIVDCGETSETGTQDAVVEEKSKSATLKprolyl cis-trans isomerase AKKKRSARDSSSESRGKRRQRKSRKERTRKRRRYSSSDSsignature is in bold. YSSESSDSDSESYSSDTESESKSHSESSVSDSSSSDGRRRKRKSTKREKLRRQRGKDSRGEQKSARYDKKSRHKSADSSSDSESESSSRSRSRDDKKKSSRRESARSVSKLKDAEANSPENLESPRDREIKKVEDNSSHEEGEFSPKNDVQHNGHGTDAKFGKYDDQRPRSDGSKKSSGSMRDSPKRLANSVPQGSPSSSPAHKASEPSSSIRARNPSRSPAPDGNSKRIRKGRGFTERFSYARRYRTPSPEDVTYRPYHYGRRNFHDRRNDRYSNYRSYSERSPHRRYRSPPRGRSPPRYQRRRSRSRSVSRSPGGNKGRYRGRDQSRSRSRSRSRSPRRGSSPANKQLPLSERLKSRLGTRVDEHSPRRRRSSSRSHDSSRSRSPDEVPDKHEGKAAPVSPARSRSSSPSGRGLVSYGDASPDSGIN 49 The amino acid sequence ofSEQ ID MSVLLVTSLGDIVVDLHADRCPLTCKNFLKLCRIKYYNG 315. The conservedcyclophilin- CVFHTVQKDFTAQTGDPTGTGTGGDSVYKFLYGDQARFF typepeptidyl-prolyl cis-trans MDEIHLDLKHSKTGTVAMASGGENLNASQFYFTLRDDLDisomerase signature is underlined.YLDGKHTVFGEVAEGLETLTRINEAYVDEKGRPYKNIRI The CCHC type zinc finger is inRHTYILDDPFDDPPQLAELIPDASPEGKPKDEVVDDVRL bold and the RNA-binding regionEDDWVPLDEQLGPAQLEEAIRAKEAHSRAVVLESIGDIP RNP-1 (RNA recognition motif) isDAEIKPPDNV

in bold/italics.

DFSQSVAKLWSQFKRKDSQAAKGKGCFKCGAPDHMARECPGSSTRQPLSKYILKEDNAQRGGDDSRYEMVFDEDAPESPSHGKKRRGRDDRDDRHKMSRQSVEETKFNDREGGHSVDKHRQSERSKHREDEMSRDSKASEAGRRRIDRDFPEEERDGEKYTESHRDRDGKRGDYRDYRKGRADVQTHGDRRGDENYRRKSAAYDDGHEGAGAARRKDSNDDHHAYRRGYGDSRKGTRDEDDDGRGRRDDPSYRRSSGHKDSSNGGREEQ KYRSGETDGKSHPERSHRGDRRR 50 Theamino acid sequence of SEQ ID MRPFNGGSSIACLVLVIAAGALAESQGPHLGSARVVFQT316. The conserved cyclophilin- NYGDIEFGFFPGVAPRTVDHIFKLVRLGCYNTNHFFRVDtype peptidyl-prolyl cis-trans KGFVAQVADVANGRTAPMNDEQRTEAEKTIVGEFSNVKHisomerase signature is underlined.VRGILSMGRYDDPDSAQSSFSILLGDAPHLDGKYAIFGRVTKGDETLKKLEQLPTRREGMFVMPTERITILSSYYYDT GAESCEEENSTLRRRLAASAVEVERQRMKCFP51 The amino acid sequence of SEQ IDMPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL 317. The conserved cyclophilin-CTGEKGTGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN type peptidyl-prolyl cis-transGTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS isomerase signature isunderlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS and thecyclophilin-type peptidyl- GRTSKPVVIADSGQLA prolyl cis-trans isomerasesignature is in bold. 52 The amino acid sequence of SEQ IDMRFTSITSAIALFAAAASALDKPLDIKVDKAVECSRKTK 318. The conserved FKBP-typeAGDKIQVHYRGTLEADGSEFDASYKRGQPLSFHVGKGQV peptidyl-prolyl cis-transIKGWDQGLLDMCPGEKRTLTIQPDWGYGSRGMGPIPANS isomerase signature isunderlined VLIFETELVEIAGVAREEL and the FKBP-type peptidyl-prolylcis-trans isomerase signature 2 is in bold. 53 The amino acid sequenceof SEQ ID MGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRAL 319. The conservedcyclophilin- CTGEKGAGRSGKPLHYKGSSFHRVIPGFMCQGGDFTAGN typepeptidyl-prolyl cis-trans GTGGESIYGSKFADENFVKKHTGPGVLSMANAGPGTNGSisomerase signature is underlinedQFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSS andThe cyclophilin-typepeptidyl- GRTSKPVVVADCGQLS prolyl cis-trans isomerase signature 2 is inbold. 54 The amino acid sequence of SEQ IDMAVATRSRWVAMSVAWILVLFGTLALIQNRLSDTGASSD 320. The conserved FKBP-typePKLVHRKVGEEKKKPDDLEEVTHKVFFDVEIGGKPAGRI peptidyl-prolyl cis-transVMGLFGKTVPKTVENFRALCTGEKGIGKSGKPLNYKGSQ isomerase signature isunderlined FHRIIPKFMIQGGDFTLGDGRGGESIYGNKFSDENFKLK and theCyclophilin-type peptidyl- HTDAGRLSMTNAGPDTNGSQFFITTVTTSWLDGRHVVFGprolyl cis-trans isomerase KVLSGMDVVHKIEAEGGQSGQPKSIVVISDSGELDLsignature is in bold. 55 The amino acid sequence of SEQ IDMAVTLHTNLGDIKCEIFCDEVPKAAEHNARGILSMANSG 321. The conserved cyclophilin-PNTNGSQFFIAYAKQPHLNGLYTIFGRVIHGFEVLDIME type peptidyl-prolyl cis-transKTQTGPGDRPLAEIRLNRVTIHANPLAG isomerase signature is underlined 56 Theamino acid sequence of SEQ ID MAVATRSRWVAMSVAWILVLFGTLALIQNRLSDTGASSD322. The conserved FKBP-type PKLVHRKVGEEKKKPDDLEEVTHKVFFDVEIGGKPAGRIpeptidyl-prolyl cis-trans VMGLFGKTVPKTVENFRALCTGEKGIGKSGKPLNYKGSQisomerase signature is underlinedFHRIIPKFMIQGGDFTLGDGRGGESIYGNKFSDENFKLK and the Cyclophilin-typepeptidyl- HTDAGRLSMANAGPDTNGSQFFITTVTTSWLDGRHVVFG prolyl cis-transisomerase KVLSGMDVVHKIEAEGGQSGQPKSIVVISDSGELDL signature is in bold. 57The amino acid sequence of SEQ IDMGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRAL 323. The conserved cyclophilin-CTGEKGAGRSGKPLHYKGSSFHRVIPGFMCQGGDFTAGN type peptidyl-prolyl cis-transGTGGESIYGSKFADENFVKKHTGPGVLSMANAGPGTNGS isomerase signature isunderlined QFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSS andThecyclophilin-type peptidyl- GRTSKPVVVADCGQLS prolyl cis-trans isomerasesignature 2 is in bold. 58 The amino acid sequence of SEQ IDMSPVAANAMEEAAEPEVPAPVTPSKDDADTDAAVSRFLG 324. The conserved A-box of theFCKSKLGLAEGNCVQSSTLLRKTAHVLRSSGTVIGTGTA Retinoblastoma-associatedprotein EEAERYWFAFVLYTVRRVGERKAEDEQNGSDETEVPLSR is underlined and theB-box of the ILKASVLNLIDFFKEIPQFVIKAGAIVSGIYGANWDSRLRetinoblastoma-associated proteinEAREMQTNYVHLCILCKFYKRICGEFFILNDAKDDMKSA is in bold.DSSTSDPVIMYQPFGWLLFLALRIHALSRFKDLVSSTNALVSVLAILIIHLPTRFRKFSISDSSQLVKRSEKGVDLVGSLAYRYDTSEDEIKRTLEKANNVIAEILGITPPPASECKAENLENVDTDGLIYFGNLMEETSLSSILSTLEKIYEDATRNDSEFDERVFINDDDSLLVSGSLSGAAINLTGAKRKYDSFASPAKTITRPLSPSRSPASHINGIIGGTNLRITATPVATAMTTAKWLRTFVSPLPSKPSTDLQGFLASCDRDVTSDVIRRANIILEAIFPNSPIGERTVTGGLQNANLMDNMWAEQRRLEALKLYYRVLEAMCRAEAQILHSNNLTSLLTNERFHRCMLACSAELVLATHKTVTMLFPAVLERTGITAFDLSKVIESFVRHEETLPRELRRHLNTLEERLLENMVWERGSSMYNSLVVARPALAPEINRLGLLPEPMPSLDAIALLINFSSSGLPQSPVQKHEASPGQNGDIRSPKRISTEYRSVLVERNFTSPVKDRLLALSNIKSKLPPPPLQSAFASPTRPHPGGGGETCAETAIHIFFSKITKLAAVRINAMLERLQLSQQIKEGVYCLFQQILSQRTNLFFNRHIDQVILCCFYGVAKINQINLTFREIIYNYRKQPQCKPQVFRNVFVDWSTRRNGKAGNEHVDIISFYNEIFIPSVKPLLVELGPTGATTRTNRTSEVGNKNDAQCPGSPKISSFPTLPDMSPKKVSASHNVYVSPLRSSKMDASISHSSKSYYACVGESTHAYQSPSKDLVAINSRLNGNRKVRGTLNFDDVDAGLVSDSMVANSLYLQNGSSM SSSTAKSSEK 59 The amino acidsequence of SEQ ID MRPILMKGHERPLTFLKYNREGDLLFSCAKDHTPTVWFA 325. Theconserved G-protein beta DNGERLGTYRGHNGAVWCCDVSRDSMRLITGSADTTAKL WD-40repeat domains are WSVQNGTQLFTFNFDSPARSVDFSIGDKLAVITTDPFME underlined.LPSAIHVKRIARDPADQASESVLVLRGHQGRIARAVWGPLNKTIISAGEDAVIRIWDSETGKLLRESDKETGHKKAVTSLMKSVDGSHFVTGSQDKSAKLWDIRTLTLIKTYVTERPVNAVTMSPLLDHVVLGGGQDASAVTMTDHRAGKFEAKFFDKILQEEIGGVKGHFGPINALAFNPDGKSFSSGGEDGYV RLHHFDPDYFNIKI 60 The amino acidsequence of SEQ ID MDKKR TVVPLVCHGHSRPVVDLFYSPITPDGFFLISASK 326. Theconserved G-protein beta DSSPMLRNGETGDWIGTFEGHKGAVWSCCLDTNALRAAS domainis underlined and the WD-40 GSADFSAKLWDALSGDELHSFEHKHIVRSCAFSEDTHLLrepeat domains are in bold LTGGVEKILRIFDLNRPDAPPREVDNSPGSIRTVAWLHSDQTILSSCTDIGGVRLWDVRSGKIVQTLETKSPVTSSEVSQDGRYITTADGSTVKFWDANHFGLVKSYNMPCNIESASLEPKLGNKFIAGGEDMWVHIFDFHTGEEIGCNKGHHGPV HCVRFSPGGESYASGSEDGTIRIWQTGPANNVEGDANPS NGPVTGKAKVGADEVTRKVEDLQIGKEGKDWREG 61 The amino acidsequence of SEQ ID MAEGLILKGTMRAHTDMVTAIAIPIDNSDMVVTSSRDKS 327. Theconserved G-protein beta IILWHLTKEEKVYGVPRRRLTGHSHFVQDVVLSSDGQFA1 WD-40repeat domains are LSGSWDGELRLWDLATGVSARRFVGHTKDVLSVAFSIDN underlined.RQIVSASRDRTIKLWNTLGECKYTIQEGEAHTDWVSCVRFSPNTLQPTIVSASWDRTIKVWNLTNCKRNTLAGHNGYVNTVAVSPDGSLCASGGKDGVILLWDLAEGKRLYNLEAGAIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVEDLRVDLKNEADKTDGTTTAASNKKVIYCTSLNWSADGSTLFSG YNDGVIRVWGTGRY 62 The amino acidsequence of SEQ ID MAEGLHLKGTMKAHTDMVTAIAVPIDNADMIVTSSRDKS 328. Theconserved G-protein beta IILWHLTKEDKVYGVPRRRLTGHSHFVQDVVLSSDGQFA WD-40repeat domains are LSGSWDGELRLWDLATGVSARRFVGHTKDVLSVAFSIDN underlined.RQIVSASRDRTIKLWNTLGECKYTIQEGEAHNDWVSCVRFSPNTLQPTIVSASWDRTVKVWNLTNCKLRNTLQGHSGYVNTVAVSPDGSLCASGGKDGVILLWDLAEGKKLYSLEAGAIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVEDLRVDLKNEADMSDGTTGAMSSNKKVIYCTSLNWSADGSTLFS GYNDGVIRVWGIGRY 63 The aminoacid sequence of SEQ ID MAEGLHLKGTMKAHTDMVTAIAVPIDNADMIVTSSRDKS 329. Theconserved G-protein beta IILWHLTKEDKVYGVPRRRLTGHSHFVQDVVLSSDGQFA WD-40repeat domains are LSGSWDGELRLWDLATGVSARRFVGHTKDVLSVAFSIDN underlinedand the Trp-Asp (WD) RQIVSASRDRTIKLWN TLGECKYTIQEGEAHNDWVSCVR repeatssignature is in bold. FSPNTLQPTIVSASWDRTVKVWN LTNCKLRNTLQGHSGYVNTVAVSPDGSLCASGGKDGVILLWDLAEGKKLYSLEAGAIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVEDLRVDLKNEADMSDGTTGAMSSNKKVIYCTSLNWSADGSTLFS GYNDGVIRVWGIGRY 64 The aminoacid sequence of SEQ ID MSGVPAPPFATTTPENGTMSSNSPAFHRDSDDDDDQGEV 330. Theconserved G-protein beta FLDDSDIIHEVAVDDEDLPDADDEADEAEEADDSLHIFT WD-40repeat domains are GHNGEVYSLACSPTDATLVATGAGDDKGFLWRIGHGDWA underlined.VELQGHKDSISSLAFSLDGQLLASGSLDGVIQIWDVPSGNLKGTLDGPGGGIEWIRWHPKGHIILAGSEDSTVWMWNADKMAYLNMFSGHGNSVTCGDFTPDGKTICTGSDDATLRIWNPKSGENIHVVKGHPYHAEGLTSMAISSDSGLAITGAKDGSVRIVNISSGRVVSSLDAHADSVEFVGLALSSPWAATGSLDQKLIIWDLQHSSPRATCDHEDGVTCLSWVGASRFLASGCVDGKVRVWDSLSGDCVRTFHGHSDAIQSLSVSANE EFLVSVSIDGTARVFEIAEFH 65 Theamino acid sequence of SEQ ID MGTSQHQLSSCLQLLPRRRGNKNLIFRRTMASGGAAAVA331. The conserved G-protein betaPPPGYKPYRHLKTLTGHVAAVSCVKFSNDGTLLASASLD WD-40 repeat domains areKTLIIWSSAALSLLHRLVGHSEGVSDLAWSSDSHYICSA underlined.SDDRTLRIWSSRSPFDCLKTLRGHTDFVFCVNFNPQSSLIVSGSFDETIRIWEVKTGRCLNVIRAHSMPVTSVHFNRDGSLIVSGSHDGSCKIWDTKNGACLKTLIDDTVPAVSFAKFSPNGKFILVATLNDTLKLWNYATGKFLKIYTGHKNSVYCLTSTFSVTNGKYIVSGSEDRCICIWDLQGKNLIQKLEGHSDTVISVTCHPSENKIASAGLDSDRTVRIWLQDA 66 The amino acid sequence of SEQ IDMPSQKIETGHQDIVHDVAMDYYGKRVATASSDTTIKIIG 332. The conserved G-proteinbeta VSNSSGSQHLASLSGHKGPVWQVAWAHPKFGSILASCSY WD-40 repeat domains areDGQVILWKEGNQNDWAQAHVFNDHKSSVNSIAWAPHELG underlined.LCLACGSSDGNISVFTARPDGGWDTTRIEQAHPVGVTSVSWAPSMAPGALVGSGLLDPVQKLASGGCDNTVKVWKLYNGTWKMDCFPALQMHSDWVRDVAWAPNLGLPKSTIASASQDGTVVIWTVAKEGEQWQGKVLKDFKTPVWRVSWSLTGNL LAVADGNNNVTLWNEAVDGEWQQVTTVEP 67The amino acid sequence of SEQ IDMKIAGLKSVENAHDESVWAAAWVPATESRPALLLTGSLD 333. The conserved G-proteinbeta ETVKLWRPDELALERTNAGHFLGVVSVAAHPSGVIAASA WD-40 repeat domains areSIDSFVRVFDVDTNATIATLEAPPSEVWQMQFDPKGTTL underlined and the Trp-Asp (WD)AVAGGGSASIKLWDTATWELNATLSIPRPEQPKPSEKGN repeats signature is in bold.KKFVLSVAWSPDGRRLACGSMDGTISIFDVARAKFLHHLEGHFMPVRSLVFSPVEPRLLFSASDDAHVHMYDSEGKSLVGSMSGHASWVLSVDVSPDGAALATGSSDRTVRLWD LSMRAAVQTMSNHSDQVWGVAFRPMAGAGVRAGGRLASVSDD KSISLYDYS 68 The amino acidsequence of SEQ ID MEIDLGNLAFDVDFHPSEQLVASGLITGDLLLYRYGDGS 334. Theconserved G-protein beta SPEKLLEVRAHGESCRAVRFINDGKAILTGSPDCSILAT WD-40repeat domains are DVETGSVVARVENAHEAAVNRLVNLTESTIATGDDNGCI underlinedand the Trp-Asp (WD) KVWDTRQRSCCNTFSAHEDFISDMTFASDSMKLVVTSGD repeatssignature is in bold. GTLSVCNLRSNKVQTRSEFSEDELLSVVIMKNGRKVVCGTQSGTLLLYSWGFFKDCSDRFVDLSPSSVDALLKLDEDRIIAGTENGLISLIGILPNRIIQPIAEHSDHPIERLAFSH DKKFLGSISHDQTLKLWDLNDILGSEDSPSSQAAIDDSD SDEMDVDANPPDSSKGNKKKHSGKGNDVGNANNFFADLGD 69 Theamino acid sequence of SEQ ID MSQQPSVILATASYDHTIRFWEAKSGRCYRTIQYPDSQV335. The conserved G-protein betaNRLEITPHKRYLAVAGNPSIRLFDVNSNTPQPVMSFDSH WD-40 repeat domains areTNNVMAVGFQYDGNWMYSGSEDGTVRIWDLRARGCQREY underlined and the Trp-Asp (WD)ESRGAVNTVVLHPNQTELISGDQNGNIRVWDLTANSCSC repeats signature is in bold.ELVPEVDTAVRSLTVMWDGSLVVAANNNGTCYVWRLLRGSQTMTNFEPLHKLQAHNGYILKCLLSPEFCEPHRYLATA SSDHTVKIWNVEGFTLEKTLIGHQRWVWDCVFSVDGAYL ITASSDTTARLWSMSTSQDIRVYQGHHKATTCCALHDGAEGSPG 70 The amino acid sequence of SEQ IDMEDAMDMEVEVEVEAEEHSPSSSNPSGSSFRRFGLKNSI 336. The conserved G-proteinbeta QTNFGSDYVFEITPKFDWSLMGVSLSSNAVKLYSPTTGQ WD-40 repeat domains areYCGECRGHSDTVNGISFSGPSSPHVLHSCSSDGTIRAWD underlined.TRSFKEVSCISAGPSQEIFSFSFGGSSDSLLSAGCKSQILFWDWRNKKQVACLEDSHVDDVTQVCFVPHHQNKLISASVDGLICIFDTAGDINDDEHMESVINVGTSIGKVGIFGQTFEKLWCLTHIETLSVWDWKEGTNEANFEDARKLASDSWSLDHIDYFVDCHSAEEGEGLWVIGGTNAGTLGYFPVKYKGGAAIGSPEAVLGGGHSDVVRSVLPMSGMAGTTSKTRGIFGWTGGEDGRLCCWLSDDSSATSRSWMSSNLVLKSSRSHH KKNRHQPY 71 The amino acidsequence of SEQ ID MSQHQEYPMEYAADDYDVGEVEDDMYFHERVMGDSDTDE 337. Theconserved G-protein beta DEEYDHLDNKITDTSAADARRGKDIQGIPWERLSVTREK domainis underlined and the WD-40 YRRTRIEQYKNYENVPQSGESSEKDCKPTRKGGNYYEFWrepeat domains are in bold RNTRSVKSTILHFQLRNLVWSTTKHDVYLMSHFSIIHWSSLTCKKTEVLDVYGHVAPREKHPGSLLEGFTQTQVSTLAVRDKLLIAGGFQGELICKNLDRPGVSYCCRTTYDDNAITNAVEIYDYPSGAVHFMASNNDCGVRDFDMEKFELSRHFTFPWPVNHTSLSPDGKLLVIVGDNPEGIVVDSQR GKTIRPLQGHLDFSFASAWHPDGHIFATGNQDKTCRIWDIRNLSKSVAVLKGNLGAIRSIRFTSDGRFMAMAEPADFVHVYD VKSGYEKEQEIDFFGEISGVSFSPDTESLFVGVWDRTYGSL LQYNRCRNYSYLDSM 72 The aminoacid sequence of SEQ ID MGASSDPNPDVSDEHQKRSEIYTYEAPWHIYAMNWSVRR 338. Theconserved G-protein beta DKKYRLAIASLLDHPAAAAAVPNRVEIVQLDDSTGEIRA WD-40repeat domains are DPNLSFDHPYPATKAAFVPDKDCQRADLLATSSDFLRIW underlined.RIADDSSRVDLRSFLNGNKNSEFCRPLTSFDWNEAEPKRIGTSSIDTTCTIWDIERETVDTQLIAHDKEVYDIAWGGVSVFASVSADGSVRVFDLRDKEHSTIIYESSEPDTPLVRLGWNKQDPRYMATIIMDSAKVVVLDIRYPTMPVVELQRHQASVNAIAWAPHSSCHICTAGDDSQALIWDLSSMAQPVEGGLDPILAYTAGAEIEQLQWSSSQPDWVAIAFSLKLQ 73 The amino acid sequence of SEQID MRGGGGGGDATGWDEDAYRESVLKEREVQTRTVFRAAFA 339. The conserved G-proteinbeta PSPSPSPSPDAVVVASSDGSVASYSISACLSDHRLQSLR WD-40 repeat domains areFADAKSQNVLEAEPACFLQGHDGPAYDVKFYGEGEDSLL underlined.LSCGDDGRIRGWMWRDITSSEAHDHSQGNSAKPVLDLVNPQSRGPWGALSPIPENNALAVDVKRGSIYAAAGDSCAYCWDVECGKIKTVFKGHSDYLHCIAARNSSSQIITGSEDGTARIWDCRSGKCVQVIDPDKDHKKGFFASVSCLALDASESWLVCGRGRDLSVWSISASDCIAKISTNAPAQDVLFDDNQILLVGAEPLISRLDMNGAVLSQIHCAPQSVFSVSLHQSG VTAVGGYGGLVDVISQFGSHLCTFRCKCI 74The amino acid sequence of SEQ IDMEAPIIDPLQGDFPEVIEEYLEHGIMKCIAFNRRGTLLA 340. The conserved G-proteinbeta AGCTDGSCIIWDFETRGVAKELRDKECTAAITSVCWSKY WD-40 repeat domains areGHRILVSASDKSLILWDVLSGEKIAHTTLQHTVLQACLH underlined.PGSSTPSICLACPFSSAPMIVDLNTGSTTALPVLTADVSNGATPLSRNKTSDTSVTYSPCNACFNKHGDLVYAGTSKGEILIIDHKNVRVCAIVLVSGGAVIKNVVFSRNGQYMLTNSNDRLIRIYKNLLPPKDGLKMLDELNESFNESDDVEKLKAIGSKCLELLHEFQDSITRVQWKAPCFSGDGEWVIGGAASRGEHKIYIWDRAGHLVKILEGPKEALMDLAWHPVHPIIISVSLTGLVYIWAKDYTENWSAFAPDFKELEENEEYVEREDEFDLVPETEKVKGLDVHEDDEVDVLTVERDSVFSDSDMSQEELCFLPAVPCLDIPEQQDKCVGSCSKLPDGNHSGSPLSVEAGQNGNASNHNSSPLEPMENSTADDTDGVRLKRKRKPSEKGLELQAEKVKKPVKPLKSSGRLSKTNKPVIDPD SSNGVYGDDGSD 75 The amino acidsequence of SEQ ID MRGVSWPEDGNNPSTSSSSQRNQQQAHAPRAVSGHAASH 341. Theconserved G-protein beta PSASNIFKLLVQREVSPRSKHSSKKLWREASKCQPYPFQ WD-40repeat domains are QSCEAVRDVRQGLISWVESASLRHLSAKYCPLVPPPRST underlined.IAAAFSPDGKILASTHGDHTVKLIDSQTGSCLKVLRGHRRTPWVVRFHPLYPEILASGSLDHEVRLWDANTAECIGSRNFYRPIASIAFHARGELLAVASGHKLYIWHYNRRGETSSPTIVLRTQRSLRAVHFHPHAAPFLLTAEVNDLDSADSAMTLATSPGYLHYPPPTVYFADAHSHERSRLADELPLMPLPLLMWPSFTRDDGRVPLQRIDGDVGLNGQQRVDSSSSVRLWTYSTPSGQYELLLSPVESGNSPSMPEETGNNAFSSAVEAEVSQSAMDTVEDMEVQPEERNTQFFSFSDPRFWELPLLHGWLVGQTQAGPRSVRQSSPGDIETQSAFGEVASVSPITSGVMPVSMDPSRFGGRSGSRYRSPGSRGVHVTGPNNDGPRDENDPQSVVSKLRSELAASLAAAASTELPCTVKLRIWPHDVKDPCAQLDLESCRLTIPHAVLCSEMGAHFSPCGRFLAACVACVLPHLESDPGLHGQVNQDVTGVATSPTRHPISAHQIMYELRIYSLEEATFGIVLASRPVRAAHCLTSIQFSPTSEHLLLAYGRRHSSLLKSIVIDGENTVPIYTILEVYRVSDMELVRVLPSAEDEVNVACFHPSVGGGLIYGTKEGKLR ILHYDSSHGLNLKSSGFLDENVPEVQTYALEC76 The amino acid sequence of SEQ IDMDSAVAIAALSLVVGAAIALLFFGNYFRKRRSEVVAMAE 342. The conserved G-proteinbeta ADLQPHPKNPSRPPPQPAAKKVHAKSHAHGADKDKNKRH WD-40 repeat domains areHPLDLNTLKGHGDSVTGLCFASDGRSLATACADGVVRVF underlined and the Trp-Asp (WD)KLDDASNKSFKFLRINLPAGGHPTAVAFGDGVSSVIVAS repeats signature is in bold.QHLSGCSLYMYGEEKPTNLDSNKQQTKLPMPEIKWEHHKVHEQKAILTLSGAAANYDSGDGSTIIASCSEGTDIIIWHAKTGKILGNVDTNQLKNTMSAISPNGRFIAAAAFTADVKVWEIVYSKDGSVKGVTKVMQLKGHKSAVTWLCFTPNSEQ IVTASKDGSIRIWNINVRYHLDEDTKTLKVFPIPLQDSS GTTLHYERLSLSPDGKILAATHGSMLQWLCIETGKVLDTAEKAHDGDITCMSWAPQSIPTGDKKVNVLATASGDKKVK LWAAPPLPS 77 The amino acidsequence of SEQ ID MEVEPKKASKTFPVKPKLKPKPRTPSGKTPESKYWSSFK 343. Theconserved G-protein beta TTHPLDNLSFSVPSLAFSPSPPHLLAAAHSATVSLFSPH WD-40repeat domains are RTTISSFSDVVSSLSFRSDGQLLAASDLSGLIQVFDVRS underlined.RTPLRRLRSHARPVRFVRYPVLDKLHLVSGGDDALVKYWDVAGESVVSELRGHKDYVRCGDCSPADANCFVTGSYDHVVKLWDVRVRDGNRAATEVNHGSPVQDVIFLPSGSLVATAGGNSVKIWDLIGGGRMVYSMESHNKTVTSICVGTMGAQQSGEEGVQLRILSVGLDGYMKVFDYSRMKVTHSMRFPAPLLSIGFSPDSNVRAIGTSNGILYVGKRKAKENAEGGANGILGLGSVEEPRRRVLKPSFYRYFHRGQSEKPSEGDYLVMRPKKVKLAEHDKLLKKFQHKNALISVLGGNDPEKVVAVMEELVARRALLKCVLNLDADELGLILTFLHKNSTVPRYSSLLLGLAKKVIDLRLEDIRASDALKGHIRNLKRSVDEEIRI QEGLQEIQGMVSPLLRIAGRR 78 Theamino acid sequence of SEQ ID MQGGSSGVGYGLKYQARCISDVKADTDHTSFLTGTLSLK344. The conserved G-protein betaEENEVHLLRLSSGGTELICEGLFSHPSEIWDLSSCPFDQ WD-40 repeat domains areRIFSTVFSTGESYGAAVWQIPELYGQLNSPQLEKIASLD underlined.AHSRKISCVLWWPSGRHDKLVSIDEENIFLWGLDCSKKSAQVQSQESAGMLHNLSGGAWDPHDVNTVAATCESSIQFWDLRTMKKANSLESVHARDLDYDMRKKHLLVTSEDESGVRVWDLRMPKAPIQEFPGHTHWTWAVRCNPDYEGLILSAGTDSAVNLWWSSTASSDELISERLIDSPTRKLDPLLHSYNDYEDSVYGLAWSSREPWIFASLSYDGRVVVESVKPFLSRK 79 The amino acid sequence ofSEQ ID MAEEEGSAELEQQLEEEFAVWKKNTPILYDLLISHALEW 345. The conservedG-protein beta PSLTVHWAPLLPQPSSSAAAAAGDPSLAAHRLVLGTHTS WD-40 repeatdomains are DGAPNFLILADALLPSSESDHCGDDAVLPKVEISQKIRV underlined.DGEVNRARFMPQNHNIVGAKTNGCEVYVFDCSKQAAKQHDGGFDPDLRLTGHDGEGYGLSWSPLKENYLLSASHDKKICLWDISAAAQDKVLGAMHVFEAHEGAVGDASWHSKNDNLFGSAGDDCQLMIWDLRTNKAQQCVKAHEKEVNSVSFNSYNDWILATASSDTTVGLFDMRKLTTPLHVFSSHEGEVLQVEWDPNHEAVLASSSEDRRVMVWDLNRIGDEQQEGDASDGPAELLFSHGGHKAKISDFSWNKNEPWVISSVAEDNSVQV WQMAESICGDDDDMQAMEGYI 80 Theamino acid sequence of SEQ ID MGNYGEEDEDQYFDALEETASVSDRGSNSSDCCSSGSGL346. The conserved G-protein betaDENVLDSLGFEFWTKFPESVRARRNRFLMLTGLGIEANS WD-40 repeat domains areVDKEDAFPPSCNEIEVYTCKVTRDDGAVQRSLDSYNCIS underlined.LLQSSTSIRSNQEVESLRGDSLLSSFRGRSKESDDLTELCGMGCPESKRNAVSEFGSVSQGSIEELRRIVASSPLVHPLLHRKLEYERELIETKQKMGAGWLRKFGSATCISGRQGDTWSDPDDLEITAGMKMRRVRAHSSKKKYKELSSLYAAQEFLAHEGSISTMKFSMDGQYLASAGEDTVVRVWKVTEEDRSERVNVTVDPSCLYFALNESTQLASLNTNKEHIGKAKTFQRSSDSSCVILPLKVFQITEKPWHEFKGHNGEVLDLSWSSKGYLLSSSTDKTVRLWRVGCDRCQRVYSHNDYVTCISFNPVNENFFISGSIDGKVRIWNVFGGQVVAYIDCREIVSAVCYRSDGKGAIVGTMTGNCLFYSIKDNHLQMDAQVYLHGKKKSPGKRITGFQFPPNDPGKLMITSADSVIRVLSGLDVVCKLKGPRNSGGPMIATFTSDGKHVISASEDSNVYIWNYAGQDKTSSRVKKIWSCESFWSSNASVALPWCGIRTVPEALAPPSRSEERRASCAENGENHHMLEEYFQKMPPYSPDCFSLSRGFFLELLPKGSATWPEEKLSDTSPPTVSSQAISKLEYKFLKSACHSVLSSAHMWGLVIVTAGWDGRIRTYHNYG LPVRS 81 The amino acid sequenceof SEQ ID MDIDFKEYRLRCELRGHEDDVRGVCVCGDGSIGTSSRDR 347. The conservedG-protein beta TVRLWAPSAGERRKYEVARVLLGHKSFVGPLAWVPPSEE WD-40 repeatdomains are LPEGGIVSGGMDTLVMAWDLRNGEAQTLKGHQLQVTGIV underlined.LDGGDIVSASVDCTLIRWKNGQLTEHWEAHKAPIQAVIRLPSGELVTGSSDTTLKLWRGKTCTQTFVGHTDTVRGLAVMPDLGILSASHDGSIRLWAVSGECLMEMVDHTSIVYSVDSHASGLIVSGSEDRFAKIWKDGVCFQSIEHPGCVWDVKFLEDGDIVTACSDGTIRIWTNQEDRMANSTELELFDLELSSYKRSRKRVGGLKLEELPGLEALQVPGTSDGQTKVIREGDNGVAYAWNSTELKWDKIGEVVDGPEDSMNRPALDGVQYDYVFDVDIGDGEPTRKLPYNRSDNPYDTADKWLLKENLPLSYRQQIVEFILANSGQRDFNLDPSFRDPYTGSSAYVPGAPSQLAAKQARPTFKHIPKKGMLVFDAAQFDGILKKINEFNNTLLSNQEKKNLSLTDIEISRLGAVVKILKDTSHYHSSKFADADFDLMLKLLESWPYEMMFPVIDIFRMVILHPDGADGLLRHQEDKKDVLMESIKRATGNPSVPANFLTSIRAVTNLFKNSAYYSWLQKHRSEMLDAFSSCSSSSNKNLQLSYATLLLNYAVLLIEKKDEEGQSQVLSAALELAENESLEVDARYRALVAIGSLMLDGLVKRIALDFDVEHIAKAARTSKE AKIAEVGADIELLIKQS 82 The aminoacid sequence of SEQ ID MEFTEAYKQSGPCCFSPNARFIAVAVDYRLVIRDTLSLK 348. Theconserved G-protein beta VVQLFSCLDKISYIEWALDSEYILCGLYKRPMIQAWSLI domainis underlined and the WD-40 QPEWTCKIDEGPAGIAYARWSPDSRHILTTSDFQLRLTVrepeat domains are in bold WSLVNTACVHVQWPKHASKGVSFTRDGKFAAICTRHDCKDYINLLSCHNWEIMGVFAVDTLDLADIQWSPDDSAIVIW DSPLEYKVLVYSPDGRCLFKYQAYESGLGVKSVSWSPCG QFLAVGSYDQMLRVLSHLTWKTFAEFTHLSNVRAPCCAAIFKEVDEPLQIDMSELSLSDDYMQGNSGDAPEGHYRVRYDVTEVPITLPCQKPPADRPNPKQGIGLMSWSNDSQYICTRNDSMPTILWIWDMRHLELAAILVQKDPIRAAVWDPTGT RLVLCTGSSHLYMWTPSGAYCVSVPLSQFNITDLKWNSD GSCLLLKDKESFCCAAAPLPPDESSDYSSDD 83 The aminoacid sequence of SEQ ID MATIAALDDDMVRSMSIGAVFSDFVGKLNSLDFHRKDDI 349. Theconserved G-protein beta LVTAGEDDSVRLYDIANARLLKTTFHKKHGTDRVCFTHH WD-40repeat domains are PNSLICSSTKNLDTGESLRYISMYDNRSLRYFKGHKQRV underlined.VSLCMSPINDSFMSGSLDHSVRMWDLRVNACQGILRLRGRPTVAYDQQGLVFAVAMEGGAIKLFDSRSYDKGPFDAFLVGGDTSEVCDIKFSNDGKSVLLSTTNNNIYVLDAYAGDKQCGFNLEPSPSTPIEASFSPDGQYVVSGSGDGTLHAWNISRRNEVACWNSHIGVASCLKWAPRRAMFVAASTVLTFWI PNSEPELASAKGEAGVPPEQV 84 Theamino acid sequence of SEQ ID MSVAELKERHRAATETVNSLRERLKQKRVQLLDTDVAGY350. The conserved G-protein betaARTQGKTPVTFGATDLVCCRTLQGHTGKVYSLDWTPERN WD-40 repeat domains areRIVSVSQDGRFIVWNALTSQKTHAIRLPCAWVMTCAFAP underlined and the betaG-protein NGQSVACGGLDSVCSIFNLNSPVDRDGNLPVSRMLSGHK (transducin) is inbold. GYVSSCQYVPDGDAHLITGSGDQTCVLWDITTGLRTSVFGGEFQSGHTADVLSVSINGSSPRIFVSGSCDSTARMWDTRVASRAVHTYHGHEGDVNAVKFFPDGNRFGTGSDDGTCRLFDIRTGHELQVYYQQRGIDEIPHVTSIAFSISGRLLIAGYSNGDCFVWDTLLAQVVLNLGSLQNSHEGRISCLGVSA DGSALCTGSWDTNLKIWAFGGIRRVT 85The amino acid sequence of SEQ IDMKKRPRGASLDQAVVDIRRREVGGLSGLSFARRLAASEG 351. The conserved G-proteinbeta LVLR LDIYNKLKGHRGCVNTVGFNLDGDIVISGSDDRHV domain is underlined andthe WD-40 KLWDWQTGKVKLSFDSGHLSNVFQAKIMPYTDDRSIVTC repeat domains are inbold AADGQARHAQILEGGQVQTMLLAKHRGRAHKLAIDPGSPHIVYTCGEDGLVQRLDLRSNTARELFTCREVYGTHVEVVHLNAIAIDPRNPNLFVIGGSDEYARVYDIRNYKWNGSHNFGRSANYFCPSHLIGEAHVGITGLAFSGQSELLVSYNDESIYLFTQEMGLGPDPLSASTKSVDSNSSEVTSPTAVNVDDNVTPQVYKGHRNCETVKGVGFFGPKCEYVVSGSDCGRIFIWKKKGGQLIRVMAADKHVVNCIEPHPHIPALASSGIE NDIKIWTPKAIERATLPMNVEQLKPKARGWMNRISSPRQ LLLQLYSLERWPEHGGETSSGLAASQEELTELFFALSANGNGSPDGGGDPSGPLL 86 The amino acid sequence of SEQ IDMSKRGYKLQEFVAHSSNVNCLSIGKKACRLFLTGGDDCK 352. The conserved G-proteinbeta VNLWAIGKPNSLMSLCGHTNAVESVAFDSAEVLVLAGAS WD-40 repeat domains areSGVIKLWDVEEAKLVRGLTGHRSNCTAMEFHPFGEFFAS underlined and the Trp-Asp (WD)GSTDTNLKIWDIRKKGCIHTYKGHTRGISTIRFSPDGRW repeats signature is in bold.VVSGGNDNVVKVWDLTAGKLLHDFKFHENHIRSIDFHPL EFLLATGSADRTVKFWDLETFELIGSSRPEAAGVRAIAF HPDGRTLFCGLEDSLKVYSWEPVICHDGVDMGWSTLADLCIHDGKLLGCSYYQSSVGVWVADASLIEPYGTNVKPQQKDSGDDEIEHQESRPSAKVGTTIRSTSIMRCASPDYETKDIKNIYVDTASGNPVSSQRVGTTNFAKVTQPLDFNDTPNLTLRRQGLVTETPDGLSGHVPSKSITQPKVVSRDSPDGKDSSRRESITFSRTKPGMLLRPAHSRRPSSTKYDVDRLSACAEIGVLSSAKSGSESLVDSFLNIKVAPEDGARNGCEDNHSSVKNVSVESEKVLPLQTPKTEKCDQTVGFKEEINSVKFVNGVAVVPGRTRTLVEKFEKREKLNSTEDQTINTPENPTLDKTPPPSLAENEEKSDRLNIVERKATRMSSHMVTAEDRTPVTLVGSPEDQSTVMAPQRELPADESSKTPPLPVEDLEIHHGSNVSEDKATILSSQTVSEEDSKRSTLIRNFRRRDRFKSTEGRSPVMATQRKLPTDESGKTSSLPMEDLEIKGGLNVSEDKATSFSSRAPPREDRAHSALVRNVRKRDKFKSTNDTITVMVHQRGLSTDEASTVSVERVERRQLSNNVENPLNNLPPHSVPPTTTRGEPQYVGSESDSVNHEDVTELLLGNH EVFLSTLRSRLTKLQVV 87 The aminoacid sequence of SEQ ID MSTFLTGTALSNPNPNKSYEVVQPPNDSVSSLSFNPKAN 353. Theconserved G-protein beta FLVATSWDNQVRCWEIVRSGTSLGTTPKASISHDQPVLC WD-40repeat domains are STWKDDGTTVFSGGCDKQVKMWPLSGGQPMTVAMHDAPI underlined.KEISWIPEMNLLVTGSWDKTLRYWDTRQANPVHIQQLPERCYALTVRHPLMVVGTADRNLIIYNLQSPQTEFKRISSPLKYQTRCLAAFPDQQGFLVGSIEGRVGVHHLDDSQQSKNFTFKCHREGSEIYSVNSLNFHPVHHTFATAGSDGAFNFWDKDSKQRLKAMSRCSQPIPCSTFNNDGSIFAYSACYDWSKGAENHNPATAKTYIFLHLPQESEVKGKPRLGTTGRK 88 The amino acid sequence of SEQID MEVEAQQRDVNNVMCQLVDPEGTTLGPPMYLPQDVGPQQ 354. The conserved G-proteinbeta LQQMVNKLLSNEDKLPYTFYISDQELVVPLESYLQKNKV WD-40 repeat domains areSVEKVLSIVYQPQAIFRIRPVNRCSATIAGHSEAVLSVA underlined and the Trp-Asp (WD)FSPDGKQLASGSGDTTVRLWD LSTQTPMFTCKGHKNWVL repeats signatures are in bold.SIAWSPDGKHLVSGSKAGEIQCWDPLTGQPSGNPLVGHKKWITGISWEPVHLSSPCRRFVSSSKDGDARIWDVTLRRCVICLSGHTLAVTCVKWGGDGVIYTGSQDCTIKVWETSQGKLIRELKGHGHWVNSLALSTEYVLRTGAFDHTGKQYSSAEEMKQVALERYKKMKGNAPERLVSGSDDFTMFLWEPSVSKHPKTRMTGHQQLVNHVYFSPDGQWVASASFDKSVKLWNGITGKFVAAFRGHVGPVYQISWSADSRLLLSGSKDSTLK IWDIRTKKLKRDLPGHADEVFAVDWSPDGEKVVSGGKDK VLKLWMG 89 The amino acid sequenceof SEQ ID MDAGSAHSSSNMKTQSRSPLQEQFLQRRNSRENLDRFIP 355. The conservedG-protein beta NRSAMDFDYAHYMLTEGRKGKENPAVSSPSREAYRKQLA WD-40 repeatdomains are ETLNMNRTRILAFKNKPPTPVELIPHELTSAQPAKPTKT underlined.RRYIPQTSERTLDAPDLLDDYYLNLLDWGSSNVLSIALGNTVYLWNASDGSTSELVTIDDETGPVTSVSWAPDGRHIAVGLNNSDVQLWDSADNRLLRTLRGGHRSRVGSLAWNNHILTTGGMDGLIVNNDVRVRSHIVDTYRGHTQEVCGLKWSASGQQLASGGNDNILHIWDRSTASSNSPTQWLHRLEEHTAAVKALAWCPFQGNLLASGGGGGDRTIKFWNTHTGACLNSVDTGSQVCALLWNKNERELLSSHGFTQNQLTLWKYPSMVKIAELTGHTSRVLFMAQSPDGCTVASAAGDETLRFWNVF GVPEVAKPAPKANPEPFAHLNRIR 90 Theamino acid sequence of SEQ ID MEEAIPFKNLPSREYQGHKKKVHSVAWNCTGTKLASGSV356. The conserved G-protein betaDQTARVWHIEPHGHGKVKDIELKGHTDSVDQLCWDPKHA WD-40 repeat domains areDLIATASGDKTVRLWD ARSGKCSQQAELSGENINITYKP underlined and the Trp-Asp (WD)DGTHVAVGNRDDELTILDVRKFKPIHKRKFNYEVNEIAW repeats signature is in bold.NMSGEMFFLTTGNGTVEVLAYPSLRPVDTLMAHTAGCYCIAIDPVGRYFAVGSADSLVSLWDISEMLCVRTFTKLEWPVRTISFNHTGDYVASASEDLFIDISNVQTGRTVHQIPCRAAMNSVEWNPKYNLLAYAGDDKNKYQADEGVFRIFGFESA 91 The amino acid sequence ofSEQ ID MGKDEEEMRGEIEERLINEEYKVWKKNTPFLYDLVITHA 357. The conservedG-protein beta LEWPSLTVEWLPDREEPPGKDYSVQKLVLGTHTSENEPN WD-40 repeatdomains are YLMLAQVQLPLEDAENDARHYDDDRADVGGFGCANGKVQ underlined.IIQQINHDGEVNRARYMPQNSFIIATKTVSAEVYVFDYSKHPSKPPLDGACSPDLRLRGHSTEGYGLSWSKFKQGHLLSGSDDAQICLWDINATPKNKSLDAMQIFKVHEGVVEDVAWHLRHEYLFGSVGDDQYLLIWDLRTPSVTKPVQSVVAHQSEVNCLAFNPFNEWVVATGSTDKTVKLFDLRKISTALHTFDAHKEEVFQVGWNPKNETILASCCLGRRLMVWDLSRIDEEQTPEDAEDGPPELLFIHGGHTSKISDFSWNTCEDWVVASVAEDNILQIWQMAENIYHDEDDVPGEESNKGS 92 The amino acid sequence of SEQ IDMMRGFSCTEDGDAPSTSSTSPPPPPPPPHRQQMQAPRAS 358. The conserved G-proteinbeta SSSSGQPTSRRSTGNVFKLLARREVSPRSKHSLKKFWGE WD-40 repeat domains areASECQLCPFQQSYEAVRDVRRSLISWVEAFSLQHLSAKY underlined.CPLMPPPRSTIAAAFSPDGKILASTHGDHTVKLIDSQTGSCLKVLRGHRRTPWVVRFHPLYPEILASGSLDHEVHLWDANTAECIGSRNFYRPIASIAFHAQGDLLAVASGHKLYIWHYNRSGETSSPTIVLRTPRSLRAVHFHPHAAPFLLTAEVNDLDLTDSAMTLATSPGYLHYPPPTIYLADAHSNERSRLEDELPLMPSPLLMWPSFTRDDGRATLPHIGGDVGLSGQQRVDSLSSGQYEFHPSPIEPSSSTSMHEEMGTDPFSSVRESEVTQSAMNIVDNTEVQPEERSTYSFSFSDPRFWELPSVYGWLVGQTQAAPRTAPSPGALETASALGEVASVSPVRSEFMPGGMDQPRLGGRSGSGCRSSGSRMMRTAGLNDHPHDENYPQSVVSKLRSELEASLAAAASTELPCTVKLRVWPYDMKDPCALFRSESCRLTIPHAVLCSEMGAHFSPCGRFFAACVACVLPQLEADPVLHGQVDPDVTGVATSPTRHPVSAYQIMYELRIYSLEEATFGMVLASRSIRAAHCLTSIQFSPTSEHLLLAYGRRHNSLLKSIVIDGENTVPIYSILEVYRVSDMELVRVLPSAEDEVNVACFHPSVGGGLVYGTKEGKLRILQ IDSSGGLNPKSTGFLDENMAEVPTYALEC 93The amino acid sequence of SEQ IDMGEGDLPRTEAGVLRGHEGAVLAARFNGDGNYCLSCGKD 359. The conserved G-proteinbeta RTIRLWNPHRGIHIKTYKSHGREVRDVHCTSDNSKLISC WD-40 repeat domains areGGDRQIFYWDVSTGRVIRRFRGHDSEVNAVKFNDYASVV underlined.VSAGYDRSVRAWDCRSHSTEPIQIINTFQDSVMSVCLTKTEIIGGSVDGTVRTFDIRIGREISDDLGQPVNCISMSNDGNCILASCLDSTLRLVDRSAGELLQEYKGHTCKSYKLDCCLTNTDAHVAGGSEDGYVFFWDLVDASVISKFRAHSSVV TSVSYHPKEDCMITASVDGTIKVWKT 94The amino acid sequence of SEQ IDMACIKGVGRSASVAMAPDGGYLATGTMAGTVDLSFSSSA 360. The conserved G-proteinbeta SLEIFGLDFQSDDRDLPLIAESPSSERFNRLSWGKNGSG WD-40 repeat domains areSDEFSLGLIAGGLVDGTIGLWNPLSLIRSEAGDKAIVGH underlinedLSRHKGPVRGLEFNVIAPNLLASGADDGEICIWDLAAPREPSHFPPLRGSGSAAQGEISFLSWNSKVQHILASTSYNGTTVVWDLKKQKPVISFSDSVRRRCSVLQWNPDLATQLVVASDEDSSPTLRLWDMRNIMSPVKEFAGHTRGVIAMSWCPNDSSYLVTCAKDNRTICWDTVTGEIVCELPAGSNWNFDVHWYPKIPGVISASSFDGKIGIYNVEGCSRYGVRENEFGAATLRAPKWFKRPVGASFGFGGKVVSFHTRSTGGPSVNSSEVFVHDIITEQTLVSRSSEFEAAIQSGDRPSLRALCEKKSQHCESTDDQETWGFLKVLLEDDGTARSKLLAHLGFDIPTETNDGSQEDLSQQVNALGLEDVTADKVVQEDNNESMVFPTDNGEDFFNNLPSPRADTPVSTSADGFPTVNAAVEPSQDEVDGLEESSDPSFDDSVQRALVVGDYKAAVALCMSANKLADALVIAHVGGASLWESTRDKYLKMSRLPYLKVVFAMVNNDLQSLVDTRPLKFWKETLAILCSFAQGEEWAMLCNSLASKLMAAGNMLAATLCFICAGNIDKTVEIWSRSLATEHDGMSYMDLLQDLMEKTIVLALASGQKQFSASVCKLVEKYAEILASQGLLTTAMDYLKLLGTDDLSPELAVLRDRIAFSVEAEKGANISAFNGSQDPRGAVYGVDQSNYGMVDTSQHYYPEAAQPQVPHTVPGSPYGENYQQPFGSSFGKGYNTPMQYQAPSQASMFVPSEPPQNAQPSFVPTPVTSQPTTRSQFIPAPPLALRNPEQYQQPTLGSHLYPGSVNPTFQPLPHAPGPVAPVPPQVSSVPGQNMPQAVAPTQMRGFMPVTNPGVVQNPGPISMQPATPIESAAAQPVVSPAAPPPTVQTADTSNVP APQKPVIATL 95 The amino acidsequence of SEQ ID MKERGKGAGRSVDERYTQWKSLVPVLYDWLANHNLVWPS 361. Theconserved G-protein beta LSCRWGPQLEQATYKNRQRLYLSEQTDGSVPNTLVIANV WD-40repeat domains are EVVKPRVAAAEHISQFNEEARSPFVKKFKTIIHPGEVNR underlined.IRELPQNSKIVATHTDSPDVLIWDVETQPNRHAVLGASTSRPDLILTGHKDNAEFALAMSPTEPFVLSGGKDRYVVLWSIQDHISTLAADPGSAKSPGSAGTNNKQSSKAAGGNDKTGDSPSIEPRGVYLGHGDTVEDVTFCPSSAQEFCSVGDDSCLILWDARTGSSPAIKVEKAHHADLHCVDWNPHDVNLILTGSADNTVRMFDRRNLTSGGVGSPVHTFEGHNAAVLCVQWSPDKSSVFGSSAEDGILNIWDHEKIGRKIETVGSKVPNSPPGLFFRHAGHRDKVVDFHWNSSDPWTIVSVSDDGESTGGGGTLQIWRMIDLIYRPEEEVLAELDKFKSHILSCTS 96 The amino acid sequence of SEQID MAKIAPGCEPVAGTLTPSKKREYRVTNRLQEGKRPLYAV 362. The conserved G-proteinbeta VFNFIDSRYFNVFATVGGNRVTVYQCLEGGVIAVLQSYI WD-40 repeat domains areDEDKDESFYTVSWACNIDRTPFVVAGGINGIIRVIDAGN underlined and the Trp-Asp (WD)EKIHRSFVGHGDSINEIRTQPLNPSLIVSASKDESVRLW repeats signature is in bold. NVHTGICILIFAGAGGHRNEVLSVDFHPSDKYRIASCGMDNTVKIWSMKEFWTYVEKSFTWTDLPSKFPTKYVQFPVFIAPVHSNYVDCNRWLGDFVLSKSVDNEIVLWEPKMKEQSPGEGSVDILQKYPVPECDIWFIKFSCDFHYHSIAIGNREGKIYVWELQSSPPVLIAKLSHPQSKSPIRQTAMSFDGST ILSCCEDGTIWRWDAITASTS 97 Theamino acid sequence of SEQ ID MNTAMHFGAGWRSIAEMGYTMSRLEIEPESCEDEKSLDG363. The conserved G-protein betaVGNSQGPNELPRCLDHELAHLTNLKSRPHEHLIRDFPGR WD-40 repeat domains areRALPVSTVKMLAGRECNYSRRGRFSSADCCHMLSRYVPV underlined.NGPSPLDQMNSRAYVSQFSADGSLFVAGFQGSHIRIYNVDKGWKCQKNILTKSLRWTITDTSLSPDQRYLVYASMSPIVHIVDIGSAAMDSLANITEIHEGLDFSADSGPYSFGIFSVKFSTDGREVVAGSSDDSIYVYDLVANKLSLRIPAHESDVNTVCFADESGHIIYSGSDDTYCKVWDRRCLSARNKPAGVLMGHLEGITFIDSRGDGRYFISNGKDQTIKLWDIRKMGSDICRRGFRNFEWDYRWMDYPPRARDSKHPFDLSVATYKGHSVLRTLIRCYFSPVHSTGQKYIYTGSHDSCVYIYDVVTGAQVAALKHHKSPVRDCSWHPEYPMIVSSSWDGDIVKW EFFGNGETEIPAMKKRIRRRHLY 98 Theamino acid sequence of SEQ ID MEPQPQAPKKRGRKPKPKEDKKEEQLHQPPPPPPPQQQA364. The conserved G-protein betaAPAPAPAATRSSTSGSAGGRDRRPQQQHAVDEKYARWKS WD-40 repeat domains areLVPVLYDWLANHNLLWPSLSCRWGPQLEQATYKNRQRLY underlined.ISEQTDGSVPNTLVIANCEVVKPRVAAAEHVSQFNEEARSPFIRKYKTIIHPGEVNRVRELPQNPNIVATHTDSPDVLIWDVESQPNRHAVYGATASRPNLILTGHQENAEFALAMCPAEPFVLSGGKDKTVVLWSIQDHITASATDQTTNKSPGSGGSIIKKTGEGNEETGNGPSVGPRGIYCGHEDTVEDVAFCPSTAQEFCSVGDDSCLILWDARVGTNPVAKVEKAHNGDLHCVDWNPHDNNLILTGSADNSVNMFDRRNLTSNGVGSPVYKFEGHKAAVLCVQWSPDKPSVFGSSAEDGLLNIWDYERVDKKVDRAPNAPAGLFFQHAGHRDKIVDFHWNAADPWTMVSVSDDCDTAGGGGTLQIWRMSDLIYRPEEEVLAELEN FKAHVLECSKA 99 The amino acidsequence of SEQ ID MGIFEPYRAVGYITTGVPFSVQRLGTETFVTVSVGKAFQ 365. Theconserved G-protein beta VYNCAKLSLVLVGPQLPKKIRALASYREYTFAAYGSDIG WD-40repeat domains are IFKRAHQLATWSGHTAKVCLLLLFGEHILSVDVDGNAYI underlinedand the Trp-Asp (WD) WAFKGMNYNLSPVGHILLDSNFTPSCIMHPDTYLNKVIL repeatssignature is in bold. The GSQEGPLQLWNISTKTKLYEFKGWNSSVSSCVSSPALDV Utp21specific WD40 associated VAVGCADGKIHVHNIRYDEELVTFSHSMRGSVTALSFSTputative domain is in italics. DGQPLLASGSSSGVVSIWNLDKRRLQSVIRDAHDGSIISLHFFANEPVLMSSSADNSIKMWIFDTSDGDPRLLRFRSGHSAPPLCIRFYANGRHILSAGQDRAFRLFSVVQDQQSRELSQRHVSKRAKKLKLKEEEIKLKPVIAFDVAEIRERDWCNVVTSHMDTPQAYVWRLQNFVIGEHILRPCPNKPTPVKACMISACGNFAILGTAGGWIERFNLQSGISRGSYIDQLEGTNSAHDGEVVGVACDATNTLMISAGYAGDIKVWDFKGRELKSRWEIGSSLVKISYHRLNGLLATVADDFIIRLFDAVALRMVRKFEGHTDRITDLCFSEDGKWLLSSSMDGSLRIWDIILARQVDAVFVDVSITALSLSPNMDILATTHVDQNGVFLWVNQSMFSGDSDINLYASGKEVVTVKLPSVSSVEGSQVEESNEPTIRHSESKDVPSFRPSLEQIPDLVTLSLLPKSQWQSLINLDIIKVRNKPVEPPKKPEKAPFFLPSIPSLSGEILFKPSEMSDKGDMKADEDKSKITPEVPSSRFLQLLHSCSEAKNFSPFTTYIKGLSPSTLDLELRMLQIIDDDAVDADADDPQDVDKRQELLSIELLMDYFIHEISCRSNFEFVQALVRLFLKIHGETIRRQSVLQNKAKVLLETQCSVWQRVDKL FQGARCMVAFLSNSQF 100 The aminoacid sequence of SEQ ID MEETKVTCGSWIRRPENVNLAVLGRSPRRRGSAALEIFA 366. Theconserved G-protein beta FDPKSTSLSSSPLVAHVIEEIEGDPLAIAVHPNGEDIVC WD-40repeat domains are FASSGSCLSFELSGQESNLKLLTKELPPLRGIGPQKCMA underlined.FSVDGSRFATGGVDGRLRILEWPSLRIILDEPKAHKSIRDLDFSLDSEFLATTSTDGSARIWKAEDGLPCTTLTRRSDEKIELCRFSKDGTKPFLFCTVQRGDKAVTGVWDISTWNKIGHKRLLRKPAVVMSISLDGKYLAQGSKDGDMCVVEVKKMEVSHWSKRLHLGTSLTSLEFCPIERVVITTSDEWGVLVTKLNVPADWKAWQVYLLLLGLFLASLVAFYIFYENSDSFWGFPLGKDQPARPKIGSVLGDPKSADDQNMWGEFGPLDM 101 The amino acid sequence ofSEQ ID MADPVEHQHQQHQQHQLQQQRRRGWRIQGGQYLGEISAL 367. The conservedG-protein beta CFLHLPPPPLSLSSSPVLSLSSGLDSESRDRPACSFRFP WD-40 repeatdomains are SAGSGSQVSLFDLASGAMVRTFYVFRGIRVHGIVLGCAD underlined.FPGGSSSSSSTLDYVIAVYGERRVKLFRLSVRLGRGAGEGSGTVLSADLELVSAAPRLSHWVMDVRFLKENGTSEDELQRCLTVAIGCSDNSIRLWDVDKCSFVLAVSSPERCLLYSMRLWGDNLEDLQVASGTIYNEILIWKVVPNHDAPSSNELTEEGLTNSCAGNSVHECLRYEAYHICRLVGHEGSIFRIAWSSDGSKLVSVSDDRSARIWEVHCKVQYSEDAGEVGLLFGHSARVWDCYISDNLIVTAGEDCSCRVWGLDGQQHDVIKEHIGRGIWRCLYDPWSSLLVTGGFDSAIKVHKLDASLAEASAKQSNIKDLSDGTELFTTHLPNSSGHSGHMDSKSEYVRCLSFSCEDVMYIATNHGYLYHAKLCNDGDLRWTELAQVSNEVQIICMELLPSNPYDPRIDADDWVAVGDGKGWTTVVRVVKNSDSPKVSTSFSWAAEMDRQLLGIHWCKSLGHRFIFTADPRGALKLWRFFEVSQSSSLYPENSPRISLIAEFKSDLGARIMCLDVAFESELLICGDLRGNLVLFPLLKDLLLDTFVVSAAKISPVNHFKGAHGISAVSSISVAHMSFNHIELRSTGADGCICYMEYDKGLQSLNFVGMKQVKELSMIESVSTENESTGYRTSGSYASGFASTDFIIWNLVTEAKVLQVSCGGWRRPHSYYLGDVPEMKNCFAYVKDDIIYIRRHWIKDSKDKILPQNLRLQFHGREVHSLCFVTGDFQLRKNKQSSWIVTGCEDGTVRLTRYTQCTDNWSSSKLLGEHVGGSAVRSICCVSNIHTTSSGTSVSDVKGIENLPKDIKGTLMEDECNPSLLISVGAKRVLTSWLLRRRKQDGKEDDVTDLQEAENSSLPSSAGSSTFSFQWLSTDMPVKYSVPSKKSGSIKKLIGV SDTNVRCKSL 102 The amino acidsequence of SEQ ID MPYKLSATLSNHSSDVRAVASPSDDLILSASRDSTAISW 368. Theconserved G-protein beta FRQSPSSFTPASVIRAGSRFVNAIAYLPPTPRAPQGYAV WD-40repeat domains are VGGQDTVVNVFALGPGDKEEPEYTLVGHTDNVCALSVNS underlined.DDTIISGSWDKTAKVWKDFALVYDLKGHQQSVWAVLAMNEKEFLTASADRTIKYWVQHKTMQTYEGHRDAVRGLALIPDIGFASCSNDSEIRVWTMGGDVVYTLSGHTSFVYSLSVLPNGDLVSAGEDRSVRVWRDGECSQVIVHPAISVWAVSTMPNGDIISGSSDGVVRVFSESEKRWATASELKALEDQIASQSLPSQQVGDVKKTDLPGPEALSVPGKKAGEVKMIRSGDVVEAHQWDSLASSWQKIGEVVDAIGSGRKQLHDGKEYDYVFDVDIQEGAPPLKLPYNVSENPYTAAQRFLEQNDLPTGYLDQVVKFIEQNTAGVKLGNDGYVDPFTGASRYQPATQSTSNTASSSYMDPFTGGSRHIAESAPSNVPQGSHATGIIPFSKPIFFKLANVSAMQAKMFQFDEVLRNEISTATLAMRPDEVIMVNETFTYLSKVVTSTSSARTSLGWIHIETIMQILDRWPVPQRFPVIDLGRLVTAYCMNAFSGPGDLEKFFSCLFRTSEWTSITSGSKALTKAQETNVLLLFRTIANSLDGAPLNDMEWIKQIFRELAQTPQLVLNKSHRLALASVLFNFSCIGLKGPVPADVRTLHLTIILQVLRSPNDDPEVAYRTCVALGNMLYSDKTRGTPRDAQSPSPTELKSAVAAIKGGFSDP RINDVHREIMSLI 103 The amino acidsequence of SEQ ID MPPQKIESGHKDTVHDLAMDYYGKRLATASSDHTINVVG 369. Theconserved G-protein beta VSSSGSQHLATLIGHQGPVWQISWAHPKFGSLLASCSYD domainis underlined and the WD-40 GRVIIWREGNPNEWTQAQVFEEHKSSVNSVAWAPHELGLrepeat domains are in bold CLACGSSDGNISVFTARQDGGWDTSRIDQAHPVGVTSVSWAPSTAPGALVGSGMMEPVQKLCSGGCDNTVKVWKLYNRVWKLDCFPVLQMHTDWVRDVAWAPNLGLPKSTIASASQDGRVIIWTLAKEGDQWQGKVLYDFRTPVWRVSWSLTGNIL AVADGNNNVSLWN EAVDGEWIQVSTVEP104 The amino acid sequence of SEQ IDMSAPMLEIEARDVVKIVLQFCKENSLHQTFQTLQSECQV 370. The conserved G-proteinbeta SLNTVDSIETFVADINSGRWDAILPQVAQLKLPRNTLED WD-40 repeat domains areLYEQIVLEMIELRELDTARAILRQTQAMGVMKQEQPERY underlined and the Trp-Asp (WD)LRLEHLLVRTYFDPNEAYQDSTKEKRRAQIAQALAAEVT repeats signature is in bold.VVPPSRLMALVGQALKWQQHQGLLPPGTQFDLFRGTAAMKQDVDDMYPTTLSHTIKFGTKSHAECARFSPDGQFLVSCSVDGFIEVWDYMSGKLKKDLQYQADETFMMHDDPVLCVDFSRDSEMLASGSQDGKIKVWRIRTGQCLRRLERAHSQGVTSVLFSRDGSQLLSTSFDGSARIHGLKSGKQLKEFRGHS SYVNDAIFSNDGSRVITASSDCTVKVWDVKTSDCLQTFK PPPPLRGGDASVNSVHLFPKNADHIVVCNKTSSIYIMTLQGQVVKSLSSGKREGGDFVAACVSPKGEWIYCVGEDRNLYCFSCQSGKLEHLMKVHEKDVIGVTHHPHRNLVATYSED STMKLWKP 105 The amino acidsequence of SEQ ID MDLLQSYAEDNDGDLGRHSSPEPSPPRLLPSKSAAPKVD 371. Theconserved G-protein beta DTTLALTVAQTNQTLARPIDPSQHAVAFNPTYDQLWAPI WD-40repeat domains are CGPAHPYAKDGIAQGMRNHKLGFVEDAAIGSFLFDEQYN underlined.TFQRYGYAADPCASTGNEYVGDLDALKQNDGISVYNIRQQEQKKYAEEYAKKKGEERGEGGREKAEVVSDKSTFHGKEERDYQGRSWIAPPKDAKATNDHCYIPKRLVHTWSGHTKGVSAIRFFPKHGHLILSAGMDTKVKIWDVFNSGKCMRTYMGHSKAVRDISFCNDGTKFLTAGYDKNIKYWDTETGKVISTFSTGKIPYVVKLHPDDEKQNILLAGMSDKKIVQWDMNTGQITQEYDQHLGAVNTITFVDDNRRFVTSSDDKSLRVWEFGIPVVIKYISEPHMHSMPSISLHPNTNWLAAQSLDNQILIYSTRERFQLNKKKRFAGHIVAGYACQVNFSPDGRFVMSGDGEGRCWFWDWKSCKVFRTLKCHEGVCIGCEWHPLEQ SKVATCGWDGLIKYWD 106 The aminoacid sequence of SEQ ID MESNGNLEQTLQDGRIYRQLNSLIVAHLRDHNFPQAASA 372. Theconserved G-protein beta VALATMTPLNVEAPRNRLLELVAKGLAVEKGELLRGVSH WD-40repeat domains are AGTNDLGGSIPASYGLVPAPWTAIDFSSLRDTKGMSKSF underlined.TKHETRHLSDHKNVARCARFSTDGRFFATGSADTSIKLFEVSKIKQMMLPDSTDGAIRAVIRTFYDHTHPVNDLDFHPQNTVLISAAKDHTVKFFDYSKATAKRAFRVIQDTHNVRSVAFHPSGDFLLAGTDHPIPHLYDVNTFQCYLSANVPEFAVNAAINQVRYSSSGGMYVTASKDGTIRFWDGASANCVRSIAGAHGAAEVTSANFTKDQRYVLSCGKDSTVKLWEVGTGRLVKQYLGATHMQLRCQAVFNNTEEFVLSIDEPSNEIVVWDAMTAEKVARWPSNHNGPPRWIEHSPTEAAFVSCSTDR SIRFWKETH 107 The amino acidsequence of SEQ ID MSNFQGEDGEYVADDFEAEDGDEELHGRESADPESDVDE 373. Theconserved G-protein beta IDTPSNRFTDTTADQARRGRDIQGIPWERLSITREKYRR WD-40repeat domains are TRLEQYKNYENVPQSGEKSGKDCTVTEKGNSFYEFRRNS underlined.RSVKSTILHFQLRNLVWATSKHDVYLMSNYSVVHWSSLTGKKSEVLNLAGHVAPNEKHPGSLLEGFTQTQVSTLAVKDRFLVAGGFQGELICKFLDRPGISFCSRTTYDDNAITNAVEIYVSPSGGIHFIASNNDCGVRDFDMENFELSKHFRFPWPVNHTSLSPDGKLLVIVGDDPEGILVDAKTGKTIMPLRGHLDFSFASEWHPDGVTFATGNQDKTCRIWDIRNLSKSIAVLKGNLGAIRSIRYTSDGRYMAIAEPADFVHVYDTKTGYKKEQEIDFFGEISGMSFSPDTESLFIGVWDRTYGSLLEY GRRRNFSYLDCLV 108 The amino acidsequence of SEQ ID MGVEEDLEDLNALAESTDAAVDGQAALASAVDSVTLQPA 374. Theconserved G-protein beta PPILPPVIPPPAVPVVAPVPTIPPVLRPLAPLPIRPPVL WD-40repeat domains are RPPAPKRDEAGSSDSDSDHDGTAAGSTAEYEITEESRLV underlinedand the splicing factor RERHEKAMQDLMMKRRGAALAVPTNDKAVRARLRRLGEP motif isin bold. MTLFGEREMERRDRLRMLMAKLDAEGQLEKLMKAHEDEEAAASAAPEDVEEEMLQYPFYTEGSKALFNARIDIAKFSITRAALRLERARRRRDDPDEDVDAEIDWALKKAESLSLHCSEIGDDRPLSGCSFSHDGKLLATCSMSGVAKLWDTCRMPQVNRVLTLKGHTERATDVAFSPVQNHIATASADRTAKLWNTEGTILKTFEGHLDRLGRIAFHPSGKYLGTTSFDKTWRLWDIESGEELLLQEGHSRSIYGIDFHRDGSLVASCGLDALARVWDLRTGRSILALEGHVKPVLGVSFSPNGYHLATGGEDNTCRIWDLRKKKSLYTIPAHANLISEVKFEPQEGYFLVTASYDTTAKVWSARDFKPVKTLSVHEAKITSVDITADA SHIVTVSHDRTIKLWTSNDDVKEQAMDVD109 The amino acid sequence of SEQ IDMVKAYLRYEPAAAFGVIASVESNIAYDASGKHLLAPALE 375. The conserved G-proteinbeta KVGVWHVRQGVCTKALAPSASSAAGPSLAVTAIASSPSS WD-40 repeat domains areLIASGYADGSIRIWDFEKGSCETTLNGHKGAVSVLRYGK underlined, and the conservedLGSLLASGSKDNDIILWDVVGETGLYRLRGHRDQVTDLV Dip2/Utp12 domain is in bold.FLDSDKKLVSSSKDKYLRVWDLETQHCMQIVGGHHSEIWSLDTDPEERYLVTGSADPELRFYTVKNDSSDERSEADASGGVGNGDLASHNKWDVLKQFGEIQRQSKDRVATVRFNKNGNLLACQAAGKLVEVFRVLDEAEAKRKAKRRLHRKREKKGADVNENSDSSRGIGEGHDTMVTVADVFKLLQTIRASKKICSISFCPVAPKSSLATLALSLNNNLLEFHSIEADKTSKMLTIELQGHRSDVRSVTLSSDNTLLMSTSHNSVKIWNPSTGSCLRTIDSGYGLCGLIVPQNKHALIGTKDGAIEIFDVGSGTCIEVVEAHGGSIRSIVAIPNQNGFVTGSADHDIKFWEYGMKQKPGDNSKHLTVSNVRTLKMNDDVLVVAVSPDAQKIAVALLDCTVKVFFMDSLKLMHSLYGHRLPVLCLDISSDGDLIVTGSADKNLMIWGLDFGDRHKSIFAHGDSIMAVQFVGNTHYMFSVGKDRLVKYWDADKFELLLTLEGHHADIWCLAISNRGDFLVTGSHDRSIRRWDRTEEPFFIEEEKEKRLEEMFESDLDNAFGNKYVPKEEIPEEGAVALAGKKTQETLSATDSIIEALDIAEVELKRIAEHEEEKNNGKTAEFHPNYVMLGLSPSDFILRALSNVQTNDLEQTLLALPFSDALKLLSYLKDWTTYPDKVELVSRIATVLLQTHYNQLVSTPAARPLLTTLKDILHKKVKECKDTIGFNLAAMDHLKQLMALRSDALFQDAKVKLLEIRSQLSKRLEERTDPREAKRRKKKQ KKSTNMHAWP 110 The amino acidsequence of SEQ ID MGGVQAEREDKDKVSLELTEEILQSMEVGMTFRDYSGRI 376. Theconserved G-protein beta SSMDFHRASSYLVTASDDESIRLYDVASATCLKTINSKK WD-40repeat domains are YSVDLVSFTSHPMTVIYSSKNGWDESLRLLSLHDNKYLR underlined.YFKGHHDRVVSLSLCPRNECFISGSLDRTVLLWDQRAEKCQGLLRVQGRPATAYDDPGLVFAIAFGGCVRMFDARKYEKGPFEIFSVGGDVSDANVVKFSNDGRLMLLTTTDGHIHVLDSFRGTLLYTFNVKPTSSKSTLEASFSPEGMFVISGSGDGSVYAWSVRGGKEVASWLSTDTEPPVIKWAPGNLMFAT GSSELSFWIPDLSKLGAYVGRK 111 Theamino acid sequence of SEQ ID MAAFGAAPAGNHNPNKSSEVIQPPSDSVSSLCFSPRANH377. The conserved G-protein betaLVATSWDNQVRCWELTKNGASVTSVPKASMSHDQPVLCS WD-40 repeat domains areAWKDDGTTVFSGGCDKQAKMWSLMSGGQPVTVAMHDAPI underlined.KEIAWIPEMNVLVTGSWDKTLKYWDTRQSNPVHTQQLPERCYAMTVRYPLMVVGTADRNLIVFNLQNPQAEFKRFSSPLKYQTRCVAAFPDQQGFLVGSIEGRVGVHHLDDSQISKNFTFKCHRDNNDIYSVNSLNFHPVHHTFATAGSDGTFNFWDKDSKQRLKAMSRCSQPIPCSTFNNDGTIYAYSVCYDWSKGAENHNPATAKTYIFLHLPQESEVKAKPRVGTTNRK 112 The amino acid sequence of SEQID MNCSISGEVPEEPVVSTKSGHVFERRLIERYVSDYGKCP 378. The conserved G-proteinbeta VSGEPLTMDDVLPVKMGKIVKPRPLQAASIPGLLSIFQN WD-40 repeat domains areEWDSLMLSNFALEQQLHTARQELSHALYQHDAACRVIAR underlined.LKKERDEARSLLALAERQIPMTASSDIAVNAPAMSNGRKASLDEEPGYAGKKMRPGISASIIAEITDCNLALSQQRKKRQIPSTLAPVEDLERYTQLSSYPLHKTGKPGITSLDICHSKDIIATGGIDTSAVLFDRSSGQIMSTLSGHSKKVTSVNFDAQGDMVLTGSADKTVRIWQGSEDGSYNCRHILKDHTAEVQAITVHATNNYFATASLDNTWCFYEFSTGLCLTQVEGASGSEGYTSAAFHPDGLILGTGTSNADVKIWDVKTQANVTTFSGHTGAITAISFSENGYFLATAAQDGVKLWDLRKLKNFRTFSAYDKDTGTNSVEFDHSGCYLGLAGSDIRVYQVASVKSEWNCVKTFPDLSGTGKVTCVKFGPDSKYIAVGSMD HNLRIFGLPSEDGAMES 113 The aminoacid sequence of SEQ ID MAAPGVETLKKEIKELKEKIAQHRLDTDGEQPLPAAAKS 379. Theconserved G-protein beta KSVPEVSAALKQRRI LKGHFGKIYALHWSADSRHLVSAS domainis underlined and the WD-40 QDGKLIIWNGFTTNKVHAIPLRSSWVMTCAYSPSGNLVArepeat domains are in bold CGGLDNLCSVYKVPHGGNKESSSAQKTYGELAQHEGYLSCCRFIKDNEIVTSSGDSTCILWDVETKTPKAIFNDHTGDVMSLAVFDDKGVFVSGSCDATAKLWDHRVHKQCVMTFQGHESDINSVQFFPDGDAFGTGSDDSSCRLFDIRAYQQINKYSSDKILCGITSVAFSKTGKSLFAGYDDYNTYVWDTLSGNQVEVLTGHENRVSCLGVSEDGKALATGSWDTLLKIWA 114 The amino acid sequence ofSEQ ID MGGVEDESEPASKRMKLSSRVLRGLANGSSRTEPAAGSS 380. The conservedG-protein beta LDLMARPLPIEGDEEVIGSKGVIKRVEFVRLIAKALYSL WD-40 repeatdomains are GYEKSGARLEEESGIPLQSSVVNLFMQQISDGLWDESVV underlined.TLHKIGLSDENLVKSASFLILEQKFLELLDQEKAMDALKTLRTEITPLCIKNSRVRELSSCIISPSSCGLLNQNKRNSTRARSRSELLEELQKLLPPAVIIPERRLEHLVEQALVLQTDACMLHNSIDMEMSLYTDHQCGKEHIPCRTLQILQSHNDEVWLVQFSHNGKYLASASNDRSAIIWEVDENGSVSLKHKLTGHQKPISSVCWSPDDRQLLTCGVGETVRRWDVSSGECLRVYEKAGHGLISCAWFPDGKWICYGVSDRSICMCDLEGKEIECWKGQRTLSISDLEITSDGKQIISICRETAILLLDREAKYERMIEENQTITSFSLSKDNRYLLVNLLNQEIHLWDIKGDFRLVAKYKGLKRSRFVIRSCFGGLKQAFVASGSEDSQVYIWHKGSGELIEPLPGHSGAVNCVSWNPANHHMLASASDDRTIRIWGLNELNTRHKGARPNGVHYCNGNGTS 115 The amino acid sequence ofSEQ ID MTQLAETYACMPSTERGRGILIAGNPKPGSNSVLYTNGR 381. The conservedG-protein beta SVVILNLDNPLDISVYAEHAYPATVARFSPNGEWVASAD WD-40 repeatdomains are SSGAVRIWGAYNDHVLKKEFKVLSGRIDDLQWSPDGLRI underlined.VASGDGKGKSLVRAFMWDSGTNVGEFDGHSRRVLSCAFKPTRPFRIVTCGEDFLVNFYEGPPFKFKLSRRDHSNFVNCLRFSPDGNRFISVSSDKKGIIYDGKTGEKIGELSSDGGHTGSIYAVSWSPDSKQVITVSADKSAKIWDISEDGSGNLRKTLTSSGSGGVDDMLVGCLWQNNHLVTVSLGGTISIYTAGDLDKAPVSFSGHMKNVSSLSVLKGDPKVILSSSYDGLIIKWIQGIGFSGRVQRKESTQIKCLAAVDEEIVTSGYDNKVCRVSGSGDAEFIDIGCQPKDLSLALQCPEFALVSTDTGVVLLRGAKIVSTINLGFAVTASTVAPDGTEAIIGAQDGKLRIYSISGDTLTEEAVLEKHRGAISVIHYSPDLSMFASGDLNREAVVWDRASREVRLKNILYHTARINCLAWSPDSSTVATGSLDTCVIIYEVDKPASNRLTIKGAHLGGVYGLAFT DDFSVVSSGEDACIRVWKINRQ 116 Theamino acid sequence of SEQ ID MKVKVISRSTDEFTRERSQDLQRVFRNFDPNLRTQEKAV382. The conserved G-protein betaEYVRALNAAKLDKVFARPFVGAMDGHVDSVSCMAKNPNY WD-40 repeat domains areLKGIFSGSMDGDIRLWDIASRRTVCQFPGHQGPVRGLAA underlined and the SOF1 proteinSTDGQILVSCGIDSTVRLWNVPVATLGESDGTHENLAKP domain is in bold.LAVYVWKNAFWAVDHQWDGELFATAGAQVDIWNQNRSQPISSFEWGTDTVISVRFNPGEPNVLATSGSDRSITLYDLRMSSPTRKVIMRTKTNAISWNPMEPMNFTAANEDCNCYSYDARKLEEAKCVHKDHVSAVMDIDYSPTGREFVTGSYDRTVRIFQYNGGHSREVYHTKRMQRVFCVKFSCDASYVISGS DDTNLRLWKAKASEQLGVVLPRERRKHEYHEAVKSRYKH LPEVKRIVRHRHLPKPIYKAGILRRTVNEADRRKEERRKAHSAPGSSSAEPLRKRRIIKEIE 117 The amino acid sequence of SEQ IDMVRSIKNPKKAKRKNKGSKNGDGSSSSSSIPSMPTKVWQ 383. The conserved G-proteinbeta PGVDKLEEGEELQCDPSAYNSLHAFHIGWPCLSFDIVRD WD-40 repeat domains areTLGLVRTEFPHQVYFVAGTQAEKPTWNSIGIFKVSNITG underlined.KRRELVPSKPTDDADEESDSSDSDEDSDDEVGGSGTPILQLRKVGHEGCVNRIRAMNQNPHICASWGDSGHVQIWDFSSHLNALAESEADVSQGASSVFNQAPLVKFGGHKDEGYALDWSPLVPGRLVSGDCKNSIHLWEPTSGSTWNVDSTPFIGHAASVEDLQWSPTEENVFASCSVDGTIAIWDTRLGKTPAASFKAHDADVNVISWNRLATCMLASGCDDGTFSIHDLRLLKEGDSVVAHFEYHKHPVTSIEWSPHEASTLAVSSADCQLTIWDLSLEKDEEEEAEFKAKTKEQVNAPEDLPPQLLFVHQGQKDLKELHWHAQIPGMIVSTAADGFNILMPSNIQST LPSDGA 118 The amino acidsequence of SEQ ID MERYKVIKELGDGTYGSVWKALNQQTHEIVAIKKMKRKY 384. Theconserved eukaryotic YIWEECINLREVKSLRKLNHPNIIKLKEVIRENNELFFI proteinkinase domain is FEYMECNLYQIMKERSTPFSETAIIKFCYQILQGLSYMH underlined andthe protein kinases RNGYFHRDLKPENLLVTSDLIKIADFGLAREVLTSPPYT ATP-bindingregion and DYVSTRWYRAPEVLLQSPTYTTAIDMWAVGAILAELFTL serine/threonineprotein kinases HPLFPGESELDEIYKICGVLGTPDYETWPDGMQLAAFRN active-sitesignatures are in FIFPQFLPVNLSVLIPHASPEAIDLITRLCSWDPQKRPT bold.AEQALHHPFFRIGMSIPLSLGGHFQDNTCAAEVDTKFHSKKACKAWNGEKESSLECFLGLSLGLKPSLGHLGAMGSQGVGAVKQEVGSSPGCQSNPKQSLFQVLNSRAILPLFSSSPNLNVVPVKSSLPSAYTVNSQVMWPTIAGPPAAAVTVSTL QPSILGDFKIFGKSMGLASQYAGKEASPFS119 The amino acid sequence of SEQ IDMGEMGRGINNSSNNNNSNRPAWLQHYDLVGKIGEGTYGL 385. The conserved eukaryoticVFLARSKLPNNRGLRIAIKKFKQSKDGDGVSPTAIREIM protein kinase domain isLLREFSHENVVKLVNVHINHVDMSLYLAFDYAEHDLYEI underlined and the proteinkinases IRHHREKLNHHNINQYTVKSLLWQLLNGLNYLHSNWIVH ATP-binding region andRDLKPSNILVMGEGEEHGVVKIADFGLARIYQAPLKPLS serine/threonine protein kinasesDNGVVVTIWYRAPELLLGAKHYTSAVDMWAVGCIFAELI active-site signatures are boxedTLKPLFQGVEVKASPNPFQLDQLDKIFKVLGHPTIEKWP in bold.TLMNLPHWSKNLQQIQQHKYDNAGLHIGPIPAKSPAYDLLSKMLEYDPRKRITAAQALEHEYFRIDPQPGRNALVPSQPGEKAINYPPRLVDANTDFDGTIAPQPSQVSSGNAPSGSIASAAVPAVRPLPQQMQLMGMQRMQNPGMAAFNLGAQASMSGLNHNNIALQRGSSQQQAHQQVRRKEPNSGFPNTGYP PPPKSRRL 120 The amino acidsequence of SEQ ID MDKYEKLEKVGEGTYGKVYKARDKMTGQLVALKKTRLEM 386. Theconserved protein kinase DEEGVPPSSLREISLLQMLSQSIYVVRLLCVEHVTKKGK familydomain is underlined. The PLLYLVFEYLDTDLKKFIDYRRSVNAGPLPQNVIQSFMYprotein kinases ATP-binding regionQLLKGVAHCHSHGVLHRDLKPQNLLVDKSKGLLKVGDLG is in bold and theLGRAFTVPLKCYTHEVVTLWYRAPEVLLGSTHYSTPVDI serine/threonine protein kinasesWSVGCIFAEMVRRQPLFPGDCEIQQLLHIFTLLGTPTEE active-site signature is inMWPGVKRLRDWHEYPQWKPENLARAVPNLSPTGLDLISK bold/italics.MLQCDPAKRISAKAAMNHPYFDDLDKSQF 121 The amino acid sequence of SEQ IDMDGYEKMDKVGEGTYGKVYMARDKKTGQLVALKKTRLEN 387. The conserved proteinkinase DGEGIPPTALREISLLQMLSQDIYIVRLLDVKHTENKLG family domain isunderlined. The KPLLYLVFEYMESDLKKYIDSYRRSHTKMPPSMIKSFMY protein kinasesATP-binding region QLCRGVAYCHSRG DKEKGVLKIADLG is in bold and theLSRAFTVPVKKYTHEIVTLWYRAPEVLLGATHYSLPVDI serine/threonine protein kinasesWSVGCIFAEMSRMQALFTGDSEVQQLMNIFRFLGTPNEE active-site signature is inVWPGVTKLKDWHIYPEWKPQDISHAVPDLEPSGLDLLSQ bold/italics.MLVYEPSKRISAKKALEHPYFDDLDKSQF 122 The amino acid sequence of SEQ IDMDAYEKLEKVGEGTYGKVYKAKDKNTGQLVALKKTRLES 388. The conserved eukaryoticDDEGIPPTALREISLLQMLSQDIHIVRLLDVEHTENKNG protein kinase domain isKPLLYLVFEYMDSDLKKYIDGYRRSHTKVPPNIIKSFMY underlined and the proteinkinases QLCQGVAYCHSRGVMHRDLKPHNLLVDKQRGVVKIADLG ATP-binding region andLGRAFTIPIKKYTHEIVTLWYRAPEVLLGATHYSTPVDI serine/threonine protein kinasesWSVGCIFAEMVRLQALFIGDSEVQQLFKIFSFLGTPNEE active-site signatures are inIWPGVTKFRDWHIYPQWKPQDISSAVPDLEPSGVDLLSK bold.MLVYEPSKRISAKKALEHPYFDDLDKSQF 123 The amino acid sequence of SEQ IDMDSYEKLEKVGEGTYGKVYKAKDKKTGKLVALKKTRLEN 389. The conserved proteinkinase DGEGIPPTALREISLLQMLSQDMNIVRLLDVEHTENKNG family domain isunderlined. The KPLLYLVFEYMDSDLKKYVDGYRRSHTKMPPKIIKSFMY protein kinasesATP-binding region QLCQGVAYCHSRG DKQRGVLKIADLG is in bold and theLGRAFTVPIKKYTHEIVTLWYRAPEVLLGATHYSTPVDI serine/threonine protein kinasesWSVGCIFAEMSRMHALFCGDSEVQQLMSIFKFLGTPNEG active-site signature is inVWPGVTKLKDWHIYPEWRPQDLSRAVPDLEPSGVDLLTK bold/italics.MLVYEPSKRISAKKALQHPYFDDLDKSQF 124 The amino acid sequence of SEQ IDMEKYEKLEKVGEGTYGKVYKGRDKRTGRLVALKKTPFHQ 390. The conserved eukaryoticEEGIPPTAIREISLLKSLSQCIYIVKLLDVKASFNGKGK protein kinase domain isHVLFMVFEYADSDLKKHIDAHRQCNTKLSPRSIQSYMFQ underlined and the proteinkinases LCKGIAYCHSHGVLHRDLKPQNILVDQKIGLLKIADLGL ATP-binding region andGRACTVPIKSYTFEVVTLWYRAPEVLLGAKRYSMALDIW serine/threonine protein kinasesSLGCIFAELCNLQALFAGDSQIQQLINIFRLLGTPNEQL active-site signatures are inWPGVTQLSDWHEFPQWRPQDLSKVVFNLDPNGVDLLSKM bold.LQYDPAKRISAKEALDHPYFDSLDKSQF 125 The amino acid sequence of SEQ IDMGCVCGKPSARAADYVESPAEKGASSNSRSSSMASRRLV 391. The conserved eukaryoticAPAVMDQGIDAENGHEGDYRTKLRGKQSNGADPVSLLSD protein kinase domain isDAEKQRHSRHHQHQQHHPIRPHHLRPQGEFVPNANSNPR underlined and theFGNPPRHIEGEQVAAGWPAWLTAVAGEAIKGWIPRRADS serine/threonine protein kinasesFEKLDKIGQGTYSNVYKARDLDTGKIVALKKVRFDNLEP active-site signatures are inESVRFMAREIQVLRRLDHPNVVKLEGLVTSRMSCSLYLV bold.FEYMDHDLAGLAACPGIKFTEPQVKCYMQQLLRGLDHCHSRGVLHRDIKGSNLLIDNGGILKIADFGLATFFHPDQRQPLTSRVVTLWYRPPELLLGATEYGVAVDLWSTGCILAELLAGKPIMPGRTEVEQLHKIFKLCGSPSEDYWKKSKLPHATIFKPQQPYKRCVAETFKDFPPSALALMEVLLAIEPADRGTATSALKSDFFTTKPLACDPSSLPKYPPSKEFDAKIRDEEARRQRAAGGRGRDAARRPSRESRAIPAPEANAELAISIQKRRLSSQGPSKSKSEKFNPQQEDGAVGFPIEPPRPMHIGIDAGATSRMYSQQFGPSHSGPLSNQISSSIWGKNQKEDEIQMAPGRPSRSSKATISDFRKPGACAPQPGADLSHLSSLVATARSNAGIDTHKDRSGMWQHNRIDAIDGVHNNGKHEFLEVPEHPNRQDWTRFQQPESFKGLDNYHLQDLPATHHRKDERVASKEATMNWQGYGGQGGDKIHYSGPLLPPSGNIDEILKEHERHIQHAVRRARQDKGRPQRSNLSQNERKAFEHRSFVSGVNGNAGYSDLVNELPISVGSNRLKVSKTRGTE EIVELRELEREPLSSVMEKYEREHEM 126The amino acid sequence of SEQ IDMGCVCAKQSDILGEPESPKVKGSNLASSRWSVSSETKQL 392. The conserved eukaryoticPQHSDSGILHHQHYYHPRDESDEAKLKESNYGGSKRRTR protein kinase domain isQGRDPADLDMGIFVRTPSSQSEAELVAAGWPAWMAAFAG underlined and serine/threonineEAIHGWIPRRAESFEKLYKIGQGTYSNVYKARDLDNGKI protein kinases active-siteVALKKVRFDSLDAESVRFMAREILVLRKLDHPNIVKLEG signatures is in bold.LVTSEVSSSLYLVFEYMEHDLAGLAACPGIKFTEPQVKCYMQQLLQGLDHCHRHGVLHRDIKGSNLLIDNGGILKIADFGLATFFYPDQKQLLTSRVVTLWYRPPELLLGATDYGVAVDIWSAGCILAELLAGKPILPGRTEVEQLHKIFKLCGSPSEDYWKESKLPHATIFKPQHPYKSCIAEAFKDFSPSALALLETLLAIEPGHRGEASGALKSEFFTTEPLSCDPSSLPKYPPSKEFDAKLRAQETRRQRDVGVRGHGSEAARRTSRLSRAGPTPNEGAELTALTQKQHSTSHATSNIGSEKPSTKKEDYTAGLHIDPPRPVNHSYETTGVSRAYDAIRGVAYSGPLSQTHVSGSTSGKKPKRDHVKGLSGQSSLQPSKPFIVSDSRSERIYEKSHVTDLSNHSRLAVGRNRDTTDPHKSLSTLMQQIQDGTLDGIDIGTHEYARAPVSSTKQKSAQLQRPSALKYVDNVQLQNTRVGSRQSDERPANKESDMVSHRQGQRIHCSGPLLHPSANIEDLLQKHEQQIQQAVRRAHHGKREALSNKSSLPGKKPVDHRAWVSSGKGNKESPYFKGKGNKELSD LKGGPTAKVTNFRQKVM 127 The aminoacid sequence of SEQ ID MAVANPGQLNLQEAPSWGSRSVNCFEKLEQIGEGTYGQV 393. Theconserved protein kinase YMAKEIETGEIVALKKIRMDNEREGFPITAIREIKLLKK familydomain is underlined. The LQHENVIKLKEIVTSPGPEKDEQGKSDGNKYNGSIYMVFprotein kinases ATP-binding regionEYMDHDLTGLAERPGMRFSVPQIKCYMKQLLIGLHYCHI is in bold and the NQ

DNNGILKLADFGLARSFCSDQNGN serine/threonine protein kinasesLTNRVITLWYRPPELLLGSTKYGPAVDMWSVGCIFAELL active-site signature is inYGKPILPGKNEPEQLTKIFELCGSPDESNWPGVSKLPWY bold/italics.SNFKPQRQMKRRVRESFKNFDRHALDLVEKMLTLDPSQRISAKDALDAEYFWTDPVPCAPSSLPRYEPSHDFQTKRKRQQQRQHDEMTKRQKISQHPPQQHVRLPPIQNAGQGHLPLRPGPNPTMHNPPPQFPVGPSHYTGGPRGAGGQNRHPQNIRPLHAAQGGGYNANRGYGGPPQQQGGGYPPHGMGNQGPRGGQFGGRGAGYSQGGPYGGPVGGRGPNVGGGNRGPQFWS EQ 128 The amino acid sequenceof SEQ ID MQNMEDNVQSSWSLHGNKEICARYEILERVGSGTYSDVY 394. The conservedeukaryotic RGRRKADGLIVALKEVHDYQSSWREIEALQRLCGCPNVV protein kinase domainis RLYEWFWRENEDAVLVLEFLPSDLYSVIKSGKNKGENGI underlined and thePEAEVKAWMIQILQGLADCHANWVIHRDLKPSNLLISAD serine/threonine protein kinasesGILKLADFGQARILEEPEAIYEVEYELPQEDIVADAPGE active-site signature is inbold. RLMEEDDSVKGVRNEGEEDSSTAVETNFGDMAETANLDLSWKNEGDMVMQGFTSGVGTRWYRAPELLYGATIYGKEIDLWSLGCILGELLILEPLFSGTSDIDQLSRLVKVLGTPTEENWPGCSNLPDYRKLCFPGDGSPVGLKNHVPSCSDSVFSILERLVCYDPAARLNAKEVLENKYFVEDPYPVLTHELRVPSPLREENNFSEDWAKWKDMEADSDLENIDEFNVVHSSD GFCIKFS 129 The amino acidsequence of SEQ ID MDLNQYPEDLNPELPEGTDNVDNPDNNKGSPVPSPHPPL 395. Theconserved eukaryotic KPLDPSERYRKGITLGQGTYGIVYKAFDTVTNKTVAVKK proteinkinase domain is IHLGKAKEGVNVTALREIKLLKELSHPNIIQLIDAYPHK underlined andthe protein kinases QNLHIVFEFMETDLEAVIKDRNLVFSPADIKSYLQMTLK ATP-bindingregion and GLAVCHKKWVLHRDMKPNNLLIAADGQLKLGDFGLARLF serine/threonineprotein kinases GSPDRKFTHQVFAVWYRAPELLFGAKQYGPAVDIWATGC active-sitesignatures are in IFAELLLRKPFLQGVSDLDQIGKIFAAFGTPRQSQWPDV bold.ASLPDFVEFQFVPAPSLRSLFPMASEDALDLLSKMFTLDPKNRITAQQALEHRYFSSVPAPTRPDLLPKPSKVDSSRPPKHASPDGPVVLSPSKARRVMLFPNNLAGILPKQVSQSTTGGTPIEFDMPTQKLREVCPRSRITESGKKHLKRKTMDMSAALDECAREQEGQEGKTILDPDHQRSAKKEKHM 130 The amino acid sequence of SEQ IDMAGGQENCVRITRARAACVSKASAPVIQSQVDEKKSRKR 396. The conserved cyclin N- andAPKRAAVDDLAANASGSQPKRRAVLGDVTNLHAAATDCL C-terminal family domains areSTAEDQVDAPNPSIKGRARNKKKEARTSTKVVKDEIHPE underlined.SNPLADHSSNLSECQKPPAAKLAEQRSLRGVPSKAKQGGSSNSQSCSKHTDIDKDHTDPQMCTTYVEDIYEYLRNAELKNRPSANFMETAQNDITPNMRAILVDWLVEVSEEYKLVPDTLYLTVSYIDRYLSANPTSRHKLQLLGVSCMLIASKYEEVCPPHVEEFCYITDNTYTRDEMLSMERKILIFLNFEMTKPTTKSFLRRFVRASQAGNKAPSLHMEFLANYLAELTLMECSFLQYLPSLIAASTVFLSRLTLDFLTNPWNPTLAHYTGYKASQLKDCVMAIYNVQMNRKGSTLVAIREKYQQHKFK CVASLPPPPFIAERFFDTPN 131 Theamino acid sequence of SEQ ID MTGTQASNVRITRARAAKSTLNNALPPLPPAQGKPRGKR397. The conserved cyclin and AATESNISGFSVAAEPLKRRAVLSDVSNICKEAAAVDCLcyclin C-terminal domains are KKPKAVKVVSQNANAKGRGRGIPRNNKKITQEAEIKKETunderlined and the cyclins SPAICNVDDASAGNAIGDDKQNNNVNPLKEVQDNPKELNsignature is in bold. PIAEQISVHPHCKQSVEKPNEKEIVVSDNKAAIASLKQQSTLQSLRIPKQPKYSLKQGNPVPLANLHEDVGRSSCSDFIDIDSEYKDPQMCTAYVTDIYANMRVVELKRRPLPNFMETTQRDINANMRSVLIDWLVEVSEEYKLVPDTLYLTVSYIDRFLSANVVNRQRLQLLGVSCMLVASKYEEICAPPVEEFCYITDNTYKKEEVLEMEISVLNRLQYDLTTPTTKTFLRRFIRAAQASCKVSSLHLEFMGNYLAELTLVEYDFLKYLPSLIAAAAVFVARMTLDPMVHPWNSTLQHYTGYKVSDMRDCICAIHDLQLNRKGCTLAAIREKYNQPKFKCVANLFPPPI ISPQFLIDNEV 132 The amino acidsequence of SEQ ID MAAPNQNALLINNNNRRPLVDIGNLVGALNAQCNISKNG 398. Theconserved cyclin and ARKRAFGDIGNLVEDLDAKCTISKYWVRKRPRTNFGVNA cyclinC-terminal domains are NKGASSSTQGQGIVVRGEQKAWDRIVWGNKQSCAIKMNAunderlined and the cyclins QHVTATQRGTAISISDIIDSSVQDGGIKAPSQLKARKQTsignature is in bold. VRTVTATLTARSEDSLRDVLEVPPGIDDGDRDNPLAVVEYVEDIYHFYRKIEVRSCVPPDYMTRQLEIKDSMRGVIIDWLIEVHRTFLLMPETLYLTVNIIDRYLSIQSVTRNELQLMGITAMFIASKYEEISPPKINDLVYITKDAYTSKQIVNMEHTILNRLKFKLTVPTPYVFLVRFLKAAGPDKVMKNLAFFLVDLCLLHYKMIKYSPSMLAAAAVYTAQCTLKKHPYWNKTLILHIGYSEAHLRECAHLMADLHLKAEGSNLKSVYKKYSYPIFGSVAFLSPAKIPAGTVAAPAIDKCAHQIYLRNLR 133 The amino acid sequence ofSEQ ID MFPNKQTQGLVQNKKMASKAAQPKAMVPPQRVPPAANNR 399. The conserved cyclinN- and RALGDIGNIVADVGGKCNVTKDGVNGKPLAQVSRPITRS C-terminal family domainsare FGAQLLAQAAANKGISAANNQTQVPVVIPKADVRGNKQR underlined.RTSKSKDIPPTTVVTNESDDCVIIEQAQRIKPTCNHNVGAVGNKEKPQLLTAKPKSLTASLTSRSAVALRGFRFDDEMTEAEEDPLPNIDVGDRDNQLAVVEYVEDIYKFYRRTEQMSCVPDYMPRQQEINPKMRAVLINWLIEVHYRFGLMPETLYLTTNLIDRYLATQLVSRSNYQLVGATAMLLASKYEEIWAPEMNDFLDILENKFERKHVLVMEKAMLNKLKFHLTVPTPYVFLVRFLKAAASDEEMENLVFFLMELSLMQYVMIKFPPSMLAAAAVYTAQITLKKTTVWNDVLKRHTGYSEIDLKECTRLMVAFHQSSEESKLNVVFKKYSMPEYDSVALIKPAK LPA 134 The amino acid sequenceof SEQ ID MAPSFDCVANAYIESCEDQEKLRQNAQILAQSGENDVDE 400. The conservedcyclin and PVSMLVQRETHYMLPEDYLQRLRNRTLDVNVRREAVGWI cyclin C-terminaldomains are LKVHSFYNFSAPTAYLAVNYLDRFLSRHRMPQGVKAWMI underlinedQLMAVACLSLAAKMEETQVPLPSDLQREDARFIFDARTIQRMELLILSTLQWGMRSITPFSFIDYFAYRAVQGHGHGHDATPKAVMSRAIELILSTTEEIDFMEYRPSAIAAAALLCAAEEVVPLQAVHYKRALSSSITDVDKDKMFGCYNLIQETIIEGGCYWTPMSLQSTEKTPVGVLDAAACLSNTPTSSYS VKPYASVTAAKRRKLNEICSALLVSQAHPC135 The amino acid sequence of SEQ IDMAANFWTSSHCKELLDAEKVGIVHPLDKDQGLTQEDVKI 401. The conserved cyclin andIKINMSNCIRTLAQYVKLRQRVVATAITYCRRVYTRKSF cyclin C-terminal domains areTEYDPQLVAPTCLYLASKAEESTVQAKLVIFYMKKYSKH underlined.RYEIKDMLEMEMKLLEALDYYLVIYHPYRPLIQFLQDAGLNDLKVTAWALVNDTYRTDLILTYPPYMIALACIYFACIMEEKDAQAWFEELRVDMNEIKNISMEIVDYYDNYRVIPD EKMNSALNKLPHRF 136 The aminoacid sequence of SEQ ID MAPALSSSYECLSHLLCAEDASNVVGCWDEDESKIFCEE 402. Theconserved cyclin domain EEGFGIQHFPDFPVPDDDEIRVLVRKESQYMPGKSYVQS isunderlined. YQNLGLDFTARQNAIGWILKVHGSYNFGPLTAYLSINYLDRFLSRNPLPKAKVWMLQLLSVACLSLAAKMEETQVPLLLDLQAEEPDFLFEPRTIQRMELLVLSTLEWRMLSVTPFSFVDYFLQGGGGRKPPPRAMVARANELIFNTHTVLDFLEHRPSAIAAAAVICAAEEVLPLEAAQYKETILSCSLVDKEWVFGSYNLIQEVLIEKFSTPKKAKSASSSIPQSPVGVLDAFCLSNNSNNTSLEASLSVNLYASVAAKRRKLNDYCNTWR MFQHSTC 137 The amino acidsequence of SEQ ID MAPNCIDCAPSDLFCAEDAFGVVEWGDAETGSLYGDEDQ 403. Theconserved cyclin domain LHYNLDICDQHDEHLWDDGELVAFAEKETLYVPNPVEKN isunderlined. SAEAKARQDAVDWILKVHAHYGFGPVTAVLSINYLDRFLSANQLQQDKPWMTQLAAVACLSLAAKMDETEVPLLLDFQVEEAKYIFESRTIQRMELLVLSTLEWRMSPVTPLSYIDHASRMIGLENHHCWIFTMRCKEILLNTLRDAKFLGLLPSVVAAAIMLHVIKETELVNPCEYENRLLSAMKVNKDMCERCIGLLIAPESSSLGSFSLGLKRKSSTINIPVPGSPDGVLDATFSCSSSSCGSGQSTPGSYDSNNSSILCISPAVIKKRK LNYEFCSDLHCLED 138 The aminoacid sequence of SEQ ID MPQIQYSEKYTDDTYEYRHVVLPPETAKLLPKNRLLNEN 404. Theconserved cyclin- EWRAIGVQQSRGWVHYAIHRPEPHIMLFRRPLNYQQNQQ dependentkinases regulatory QQAGAQSQPMGLKAQ subunit domain is underlined and thecyclin-dependent kinases regulatory subunits signature 1 is in bold. 139The amino acid sequence of SEQ IDMDQIEYSEKYYDDTYEYRHVELPPDVARLLPKNRLLTEN 405. The conserved cyclin-EWRGIGVQQSRGWVHYAIHCSEPHIMLFRRPLNYEQNHQ dependent kinases regulatoryHPEPHIMLFRRPLNCQPNHQPQAHHPT subunit domain is underlined and thecyclin-dependent kinases regulatory subunits signature 1 is in bold. 140The amino acid sequence of SEQ IDMDQIEYSEKYYDDTYEYRHVELPPDVARLLPKNRLLTEN 406. The conserved cyclin-EWRGIGVQQSRGWVHYAIHCSEPHIMLFRRPLNYEQNHQ dependent kinases regulatoryHPEPHIMLFRRPLNCQPNHQPQAHHPT subunit domain is underlined and thecyclin-dependent kinases regulatory subunits signature 1 is in bold. 141The amino acid sequence of SEQ IDMPQIQYSEKYYDDTYEYRHVVLPPDVARLLPKNRLLNEN 407. The conserved cyclin-EWRGIGVQQSRGWVHYAIHRPEPHIMLFRRHLNYQQNQQ dependent kinases regulatoryQQAQQQPAQAMGLQA subunit domain is underlined and the cyclin-dependentkinases regulatory subunits signature 1 is in bold. 142 The amino acidsequence of SEQ ID MALVETEPVTLIHPEEPKKFKKKPTPGRGGVISHGLTEE 408. Theconserved GCN5-related N- EARVKAIAEIVGAMVEGCRKGEDVDLNALKAAACRRYGLacetyltransferase family domain isSRAPKLVEMIAALPDGERAAVLPKLKAKPVRTASGIAVV underlined and the radical SAMAVMSKPHRCPHIATTGNICVYCPGGPDSDFEYSTQSYTG family domain is in bold.YEPTSMRAIRARYNPYVQTRSRIDQLKRLGHTVDKVEFILMGGTFMSLPADYRDYFIRNLHDALSGHTSSNVEEAVCYSEHSATKCIGLTIETRPDYCLGPHLRQMLSYGCTRLEIGVQSTYEDVARDTNRGHTVAAVADCFCLAKDAGFKVVAHMMPDLPNVGVERDMESFREFFENPAFRADGLKIYPTLVIRGTGLYELWKTGRYRNYPPEQLVDIIARVLALVPPWTRVYRVQRDIPMPLVTSGVEKGNLRELALARMDDLGLKCRDVRTREAGIQDIHHKIRPEVVELVRRDYCANEGWETFLSYEDTRQDILVGLLRLRKCGHNTTCPELKGRCSIVRELHVYGTAVPVHGRDADKLQHQGYGTLLMEQAERIAWKEHRSIKIA VISGVGTRHYYRKLGYELEGPYMMKYLN 143The amino acid sequence of SEQ IDMLGFRDLYTSICEHLQRASGRLPIIAAATSLISTPEIAA 409. The conserved chromo domainVEKENKAPNSVDKMGMGSADESGRFSTSNGQFMNMNNGV is underlined and theMOZ/SAS-like VKEEWKGGVPVVPSAPTTVPVITNVKLETPSSPDHDMAR protein domain isin bold. KRKLGFLPLEVGTRVLCKWRDGKFHPVKIIERRKLPNGATNDYEYYVHYTEFNRRLDEWVKLEQLELDSVETDADEKVDDKAGSLKMTRHQKRKIDETHVEGNEELDAASLREHEEFTKVKNITKIELGRYEIETWYFSPFPSEYNNCEKLYFCEFCLNFMKRKEQLQRHMRKCDLKHPPGDEIYRSGTLSMFEVDGKKNKVYAQNLCYLAKLFLDHKTLYYDVDLFLFYILCECDERGCHMVGYFSKEKHSEESYNLACILTLPPYQRKGYGKFLISFSYELSKKEGKVGTPERPLSDLGLLSYRGYWTRVLLDILKKHKSNISIKELSDMTAIKADDVLSTLQGLDLIQYRKGQHAICADPKVLDRHLKAVGRGGLEVDVCKLIWTPY KEQ 144 The amino acid sequenceof SEQ ID MGSLDESTCSEEIRDEGKDSIRTKFKVESTVNNAQNGGN 410. The conservedMOZ/SAS-like DNSKKKRAAGLPLEVGIRLLCKWRDSKLHPVKIIERRKL protein domain isunderlined. PNGFPQDYEYYVHYTEFNRRLDEWVKLEQFELDSVETDADEKIEDKGGSLKMTRHQKRKIDEIHVEEGQGHEDFDPASLREHEEFTKVKNIAKVELGRYEIETWYFSPFPPEYSHCEKLFFCEFCLNFMKRKEQLQRHMRKCDLKHPPGDEIYRNGTLSMFEVDGKKNKIYGQNLCYLAKLFLDHKTLYYDVDLFLFYVLCECDDRGCHVVGYFSKEKHSDEAYNLACILTLPPYQRKGYGKFLIAFSYELSKKEGKVGTPERPLSDLGLLSYRGYWTRILLDILKKQRGNISIKELSDMTAIKVEDVISTLQVLDLIQYRKGQHVICADPKVLDRHLKAAGIAGLEVDVS KLIWTPYKEQCG 145 The amino acidsequence of SEQ ID MASAPMVGCDDSRDKHRWVESKVYMRKGHGKGSKGNAGF 411. Theconserved bromo family NAQNSTAQVRRENDNMGNSIADNGKSEAASEGLSSLSRK domain isunderlined. QITVNQDHPPNETSSMPAVGGLQNIDTHVTFKLEGCSKQEIWELRKKLTNELEQVRGTFKKLEARELQLRGYSVSAGVNTSYSASQFSGNDMRNNGGKEVTSEVASGGAITPKQAQRESNPPRQLSISLMENNQAASDMGEKGKRTPKANQYYRNSEFVLGKDKFPPAESKKSKSTGNKKISQSKVFSKETMQVGKEFMPQKSVNEVFKQCSLLLTKLMKHKYGWVFNLPVDAQALGLHDYHTIIKRPMDLGTVKSKLEKNLYNSPASFAEDVKLTFSNAMTYNPKGHEVHTMAEQLLQLFEERWKTIYEEHLDGKMRFGSGQGLGASSSTKKLPFQDSKKNIKKSEPAGGPSPPKPKSTNHHASRTPSAKKPKAKDPHKRDMTYEEKQKLSTNLQNLPQERLELIVQIIKKRNPSLCQHDEEIEVDIDSFDTETLWELDRFVTNYKKSLSKNKKKALLADQAKRASEHGSARNKHPMIGRELPMNNKKGEQGEKVVEIDHMPPVNPPVVEVEKDGVYAKRSSSSSSSSSDSGSSSSDSDSGSSSG SESDAYAATSPPAGSNTSARG 146 Theamino acid sequence of SEQ ID MEGHSGALGFGQGFSRSSQSPNLSPSPSHSASASVTSSG412. The conserved GCN5-related N-QKRKRNEVEHAGVASNSTGMFAVPPSHIYSHLHPMSMSM acetyltransferase family domainis PMPMHNSHPSSLSESRDGALTSNDDDDNLTGGNQSQLDS underlined and thebromodomain is MSAGNTDGREDFDDEDDDDDDEEDDDEVEGDEEDQDHDP in bold.DADDDSDDGHDSMRTFTAARLDNGAPNSRNLKPKADAAGVAIAPTVKTEPILDTVKEEKVSGNNNNNSVSANNAQVAPSGSAVLLSAVKEEANKPTSTDHIQTSGAYCAREESLKREEDADRLKFVCFGNDGIDQHMIWLIGLKNIFARQLPNMPKEYIVRLVMDRSHKSVMIIKQNQVVGGITYRPYLSQKFGEIAFCAITADEQVKGYGTRLMNHLKQHARDVDGLTHFLTYADNNAVGYFIKQDFTKEIKLEKERWHGYIKDYDGGILMECKIDPKLPYTDLPAMIRWQRQTIDEKIRELSNCHIVYSGIDIQKKEAGIPRKPIKVEDIPGLKEAGWTTDQWGHSRFRLLNSPSEGLPNRQVLHAFMRSLHKAMVEHADAWPFKEPVDPRDVPDYYDIIKDPMDVKRMFTNARTYNTHETIYYKCA NR 147 The amino acid sequenceof SEQ ID MEESGNSLTSGPDGSKRRVSYFYDSDIGNYYYSQGHPMK 413. The conservedhistone PHRIRMAHSLIVHYALDEKMEVCRPNLLQSRELRVFHAD deacetylase familydomain is DYISFLQSVTPETQHEQLRQLKRFNVGEDCPVFDGLYNF underlined.CQTYAGGSVGAAIKLNNKEADIAINWSGGLHHAKKCEASGFCYVNDIVLAILELLKVHQRVLYIDIDIHHGDGVEEAFYSTDRVMSVSFHKFGDYFPGTGHLKDVGYGKGKYYSLNVPLNDGIDDESYKNLFRPIIQKVMEIYQPEAVVLQCGADSLSGDRLGCFNLSVKGHADCVRFLRSFNVPLVLVGGGGYTIRNVARCWCYETAVAVGVEPQDKLPYNEYYEYFGPDYTLHVAPSNMENQNSAKELAKIRNTLLEQLKRIQHVPSVPFQERPPDTKFPEEDEEDYEKRPKGHKWGGEYFGSESDEEQKPQNRDIDISDKPGIRRQSPPNVEAAKKIKVEEEDGDIGI VNENDGAKWPLGEAG 148 The aminoacid sequence of SEQ ID MEESGNSLTSGPDGSKRRVSYFYDSDIGNYYYSQGHPMK 414. Theconserve histone PHRIRMAHSLIVHYALDEKMEVCRPNLLQSRELRVFHAD deacetylasedomain is underlined. DYISFLQSVTPETQHEQLRQLKRFNVGEDCPVFDGLYNFCQTYAGGSVGAAIKLNNKEADIAINWSGGLHHAKKCEASGFCYVNDIVLAILELLKVHQRVYIDIDIHHGDGVEEAFYSTDRVMSVSFHKFGDYFPGTGHLKDVGYGKGKYYSLNVPLNDGIDDESYKNLFRPIIQKVMEIYQPEAVVLQCGADSLSGDRLGCFNLSVKGHADCVRFLRSFNVPLVLVGGGGYTIRNVARCWCYETAVGVEVEPQDKLPYNEYYEYFGPDYTLHVAPSNMENQNSAKELAKIRNTLLEQLKRIQHVPSVPFQERPPDTKFPEEDEEDYEKRPKGHKWGGEYFGSESDEEQKPQNRDIDISDKPGIRRQSPPNVEAAKKIKVEEEDGDIGI VNENDGAKWPLGEAG 149 The aminoacid sequence of SEQ ID MMETGGNSLPSGPDGVKRKVAYFYDPEVGNYYYGQGHPM 416. Theconserved histone KPHRIRMTHALLVQYGLHKEMQILKPYPARDRDLCRFHA deacetylasefamily domain is DDYVAFLRGITPETIQDQVKALKRFNVGDDCPVFDGLYQ underlined.YCQTYAGGSVGGAVKLNHKLCDIAINWAGGLHHAKKCEASGFCYVNDIVLAILELLKYHKRVLYVDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGDIRDIGCGKGKYYAVNVPLDDGIDDESFQSLFKPIIQQVMLVYNPEAIVLQCGADSLSGDRLGCFNLSVKGHAECVRYMRSFNVPLLMVGGGGYTVRNVARCWCYETGVAVGVEIDDKMPQHEYYEYFGPDYTVHVAPSNMENKNTKQYLDKIRSKILENINSLPCAPSAQFQVQPPDTDFPELEEEDYDERTRSHKWDGASCDSDSENGDLKHRNHDVEESAFPRHNLANISYNTKIKLEGVGTGGLDMAAGTDTKKNDESFEAMDYESGEELRQDHFASTINASQPCDPALLTGVQNQLQSTDTVKPIEQSGNAPGIPPPSVATVSTGTRPSSISRTSSLNSMSSVKQGSILGPNPPQGLNASGLQFPVPTSNSPIRQGGSYSITVQAPDKQGLQNHMKGPQNM PGNS 150 The amino acid sequenceof SEQ ID MPPKDRVAYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVL 417. The conservedhistone SYELHKKMEIYRPHKAYPVELAQFHSADYVEFLHRITPD deacetylase familydomain is TQHLFTKELVKYNMGEDCPVFENLFEFCQIYAGGTIDAA underlined.HRLNNQICDIAINWSGGLHHAKKCEASGFCYINDLVLGILELLKHHARVLYVDIDVHHGDGVEEAFYFTDRVMTVSFHKYGDMFFPGTGDVKEVGEREGKYYAINVPLKDGIDDASFTRLFKTIITKVVDIYQPGAIVLQCGADSLAGDRLGCFNLSIDGHAQCVRIVKKFNLPLLVTGGGGYTKENVARCWSVETGVLLDTELPNEIPDNDYIKYFAPDYSLKINTAGNMENLNSKTYLSAIKVQVMENLRAIQHAPSVQMHEVPPDFYIPDIDEDELNPDERMDQHTQDRQIQRDDEYYDGDNDIDHDME EAS 151 The amino acid sequenceof SEQ ID MDSSKSEEANILHVFWHEGMLNHDLGTGVFDTLEDPGFL 418. The conservedhistone EVLEKHPENADRVRNMLSILRKGPIAPYTEWHTGRAAYL deacetylase familydomain is SELYSFHRPDYVDMLAKTSTAGGKTLCHGTRLNPGSWEA underlined.ALLAAGTTLEAMRYILDGHGKLSYALVRPPGHHAQPTQADGYCFLNNAGLAVELAVASGCKRVAVVDIDVHYGNGTAEGFYERDDVLTISLHMNHGSWGPSHPQTGFHDEVGRGKGLGFNLNVPLPNGTGDKGYEHAMHELVVPAISKFMPEMIVLVIGQDSSAFDPNGRECLTMEGYRKIGQIMRQQADQFSGGRLVVVQEGGYHITYAAYCLHATLEGVLCLPHPLLSDPIA YYPEHDIYSERVTFIKNYWQGGIISTTDKRN152 The amino acid sequence of SEQ IDMEESGNALVSGPDGSKRRVTYFYDADIGNYYYGQGHPMK 419. The conserved histonePHRMRMAHNLIVHYGLHQRMEVCRPHLAQSKDIRAFHTD deacetylase family domain isDYIHFLSSVAPDTQQEQLRQLKRFNVGEDCPVFDGLFNF underlined.CQSSAGGSIGAALKLNRKDADIAINWAGGLHHAKKCEASGFCYVNDIVLGILELLKVHQRVLYIDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGHIKDVGYGKGKYYALNVPLNDGIDDESYKHLFRPIIQKVMEVYQPEAVVLQCGADSLSGDRLGCFNLSVKGHADCVRFVRSFNIPLMLVGGGGYTIRNVARCWCYETAVAVGVEPQDKLPYNEYYEYFGPDYTLYVAPSNMENLNTEKDLEKMRNVLLEQLSKIQHTPSVPFQERPPDTEFNDEEEEDMEKRSKCRIWDGEYVGSEPEEDGKLPRFDADTYERSVLKHENKRLVPVSNVEPLKRIKQEEDG AAV 153 The amino acid sequenceof SEQ ID MDLNLVSHGEEEEGVRRRKVGIVYDERMCKHATPEDQPH 421. The conservedhistone PEQPDRIRVIWDKLNSAGVLHKCVMVEAKEASEEQLAGV deacetylase familydomain is HSRKHIEVMKSIGTARYNKKKRDKLAASYSSIYFSQGSS underlined.EAALLAAGSVVEISEKVASGELDAGVAIVRPPGHHAEADKAMGFCLFNNIAIAAKHLVHERPELGVQKVLIVDWDVHHGNGTQHMFWTDPHVLYFSVHRFDAGTFYPGGDDGFYDKIGEGKGAGYNINVPWEQGKCGDADYLAVWDHVLVPVAKSYDPDMVLISGGFDAALGDPLGGCRLTPYGYSLMTKKLMEFAGGKIVLALEGGYNLKSLADSFLACVEALLKDGPGRSSVLTHPFGSTWRVIQAVRKELSSFWPALNEELQLPRLLKDASESFDKLSSSSSDESSASEDEKKFAEVTSIMEVSPDPSSILALTAEDIAQPLAGLKIEEAGTDSQRSSDHTLLDLTNDDTQKLKQFEGEIFVMIGDEESVPSASSSKDQNESTVVLSKSNIKAHSWRLTFSSIYVWYASYGSNMWNPRFLCYIEGGQVEGMAKRCCGSEDKLLLKGYSGKLFLIECFLGDHTQIH GVQEECPFLIQIVVIRVKRMSACIK 154The amino acid sequence of SEQ IDMADEDLDLSDVGEVEDEPGEEIESTPPLAVGQEKEINSL 422. The conserved FKBP-typeALKKKLLKVGTRWETPENGDEVTVHYTGTLPDGTKFDSS peptidyl-prolyl cis-transRDRGEPFTFKLGQGQVIKGWDQGIVTMKKGERALFTIPP isomerase signature isunderlined ELAYGSSGVRPTIPPNATLQFDVELLSWTNIVDVCNDGG and the FKBP-typepeptidyl-prolyl ILKRIISEGEKYERPKDPDEVTVKYEAKLEDGTLVAKSP cis-transisomerase signatures 1 EEGVEFYVNDGHFCPAIAKAVKTMKRGESVILTIKPTYA and 2 arein bold. FGERGKDAEEGFAAIPPNATLTTSLELVSFKAVIAVTEDKKVIKKILKEADGYDKPSDGTVVQIRYTAKLQDGTIFEKKGYEGEEPFQFVVDEEQVIAGLDKAVETMKTGEIALITIGAEYGFGNFETQRDLAVIPPNSTLIYEVEMISFTKEKESWDMDTTEKIEASKQKKEQGNSLFKVGKYQRAAKKYEKAAKYIEHDSSFSAEEKKQSKVLKVSCNLNHAACRLKLKDFKEAVKLCSKVLELESQNVKALYRRAQAYIETADLDLAEFDIKKALEIEPQNREVQLEYKILKQKQIEYNKKDAKLYGNM FAKLNKLEAFEGKVLS 155 The aminoacid sequence of SEQ ID MADEGLELSDVAEVEDEPGEEFESAPPLVVGQEKELNSS 423. Theconserved FKBP-type GLKKKLLKAGTRCETPENGDEVTVHYTGTLLDGTKFDSSpeptidyl-prolyl cis-trans RDRGEPFTFNIGQGQVIKGWDQGIVTMKKREHALFTIPPisomerase family domains are ELAYGASGMPPTIPPNATLQFDVELLSWTNIVDVCKDGGunderlined. The FKBP-type ILKRIISDGEKYERPKDPDEVTVKYEAKLEDGMLVAKSPpeptidyl-prolyl cis-trans EEGVEFYVNDGNFCPAIVKAVKTMKKGENVTLTIKPAYAisomerase signatures 1 and 2 are FGEQGKDAEEGFAAIPPNATITINLQLVSFKAVKEVTEDin bold. The TPR repeat is in KKVIKKILKEADGYDKPSDGTVVQIRYTAKLQDGTIFEKbold/italics. KGYAGEEPFQFVVDEEQVIAGLDKAVETMKTGEVALITIGPEYGFGNIETQRDLAVIPPYSTLIYEVEMVSFTKEKESWDMNTTENIEASKQKKEQGNSLFKVGKYLRAAKKYDKAAKYIEHDNSFSAEEKKQSKVLKVSCNLNHAACCLKLKDFK KAVKLCSKVLELESQN

REVRLEYLILKQKQIEYNKKDAKLYGNM FARQNKLEAIEGKD 156 The amino acid sequenceof SEQ ID MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL 424. The conservedcyclophilin- CTGEKGTGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN typepeptidyl-prolyl cis-trans GTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGSisomerase signature is underlinedQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS and the cyclophilin-typepeptidyl- GRTSKPVVIADSGQLA prolyl cis-trans isomerase signature 2 is inbold. 157 The amino acid sequence of SEQ IDMPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL 425. The conserved cyclophilin-CTGEKGNGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN type peptidyl-prolyl cis-transGTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS isomerase signature isunderlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS and Thecyclophilin-type peptidyl- GRTSKPVVIADSGQLA prolyl cis-trans isomerasesignature 2 is in bold. 158 The amino acid sequence of SEQ IDMPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL 426. The conserved cyclophilin-CTGEKGTGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN type peptidyl-prolyl cis-transGTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS isomerase signature isunderlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS and Thecyclophilin-type peptidyl- GRTSKPVVIADSGQLA prolyl cis-trans isomerasesignature 2 is in bold. 159 The amino acid sequence of SEQ IDMPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL 427. The conserved cyclophilin-CTGEKGTGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN type peptidyl-prolyl cis-transGTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS isomerase signature isunderlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS and Thecyclophilin-type peptidyl- GRTSKPVVIADSGQLA prolyl cis-trans isomerasesignature 2 is in bold. 160 The amino acid sequence of SEQ IDMADDFELPESAGMMENEDFGDTVFKVGEEKEIGKQGLKK 428. The conserved FKBP-typeLLVKEGGSWETPETGDEVEVHYTGTLLDGTKFDSSRDRG peptidyl-prolyl cis-transTPFKFKLGQGQVIKGWDQGIATMKKGENAVFTIPPDLAY isomerase signature isunderlined GESGSQPTIPPNATLKFDVELLSWASVKDICKDGGIFKK and the FKBP-typepeptidyl-prolyl IIKEGEKWEHPKEADEVLVKYEARLEDGTVVSKSEEGVE cis-transisomerase signature 1 is FYVKDGYFCPAFAIAVKTMKKGEKVLLTVKPQYGFGHQG in boldand underlined. The TPR REAIGNDVARSTNATLLVDLELVSWKVVDEVTDDKKVLK repeatis in bold/italics. KILKQGEGYERPNDGAVVKVKYTGKLEDGTIFEEKGSDEEPFEFMAGEEQVVDGLDRAVMTMKKGEVALVSVAAEYGYQTEIKTDLAVVPPKSTLIYEVELVSFVKEKESWDMNTAEKIEAAGKKKEEGNALFKVGKYFRASKKYEKATKYIEYDT SFSEEEKKQSKPLK

RDVKLEYRALKEKQKEYNKKEAKFYGNMFARMSKL EELESRKSGSQKVETANKEEGSDAMAVDGESA 161The amino acid sequence of SEQ IDMAASLTPLGAGLAYATIYDQAKVRKLEPTKRSLIALCQH 429. The conserved FKBP-typeSDSQHRRFITRKYHVNVQILNRRDAIRLIGLAAGLCIDL peptidylprolyl isomerase domainis SLMYDARGAGLPPQENAKLCDTTCEKELENAPMITTESG underlined.LQYKDIKIGNGPSPPIGFQVAANYVAMVPSGQVFDSSLDKGQPYIFRVGSGQVIKGLDEGLLSMKVGGKRRLYIPGPLAFPKGLNSAPGRPRVAPSSPVIFDVSLEFIPGLESEEE 162 The amino acid sequence ofSEQ ID MSAASLSADMAIRGTILGKTALHVLGPQVVSQCRQPVMF 430. The conservedFKBP-type KCPPHTLRKMRFSAQDLQSKNFYSGFTPFKSVFISTSKR peptidylprolylisomerase domain is SWQAGSARAMSQDAAFQSKVTTKCFLDIEIGGDPAGRIV underlinedand the Cyclophilin- LGLFGEDVPKTAENFRALCTGEKGFGYKGSSFHRIIKDF typepeptidyl-prolyl cis-trans MLQGGDFDRGDGTGGKSIYGRTFEDENFKLAHVGPGVLSisomerase signature is in bold. MANAGPNTNGSQFFICTVKTPWLDKRHVVFGQVIEGMEIVKKLESEETNRTDRPKRPCRIVDCGELP 163 The amino acid sequence of SEQ IDMGRIKPQTLLQQSKKKKVPGRISVSTIIVCNLIIIFLMF 431. The conserved FKBP-typeSLVGIYRQRAKRNRATSRSDGDEEMENFGRSKINSVPHQ peptidylprolyl isomerase domainis AIVNTTKGLITLELFGKSSAHTVEKFVEWSERGYFNGLP underlined.FYRVIKHFVIQVGDPKFAGNREDWTVGGQLNVQLEFSPKHEAFMLGTSKLEDQGDGFELFITTAPIPDLNDKLNVFGRVIKGQDVVQEIEEVDTDEHFQPKSPIIINDVRLKDEL 164 The amino acid sequence of SEQID MARQSTLLLFWSLVFLGAIVFTQAKHEELEEVTHKVYFD 432. The conservedcyclophilin- VDIAGKPAGRVVIGLFGKAVPKTVENFRALCTGEKGVGK typepeptidyl-prolyl cis-trans SGKPLHYKGSFFHRIIPSFMIQGGDFTLGDGRGGESIYGisomerase signature is underlinedTKFADENFKLKHTGPVFITTVTTDWLDGRHVVFGKIISG and the cyclophilin-typepeptidyl- MDVVYKVEAEGRQSGQPKRKVKIADSGELSMD prolyl cis-trans isomerasesignature is in bold. 165 The amino acid sequence of SEQ IDMEMDEIQEQSQPQSSEKQDISQESDTGNDKTINAEKITS 434. The conserved FKBP-typeENAEVEEDDMLPPKVNTEVEVLHDKVTKQIIKEGSGNKP peptidyl-prolyl cis-transSRNSTCFLHYRAWAESTMHKFQDTWQEQQPLELVLGREK isomerase signature isunderlined KELSGFAIGVAGMKAGERALLHVDWQLGYGEEGNFSFPN and the TPR repeat isin bold. VPPRANLIYEAELIGFEEAKEGKARSDMTVEERIEAADRRRQQGNELFKEDKLAEAMQQYEMALAYMGDDFMFQLFGKYKDMANAVKNPCHLNMAQCLLKLNRYEEAIGQCNMVLAEDEKNIKALFRRGKARATLGQTDDAREDFQKVRKFSPEDKAVIRELRLLAEHDKQVYQKQKEMFKGLFGQKPEQKPKKL HWFVVFWQWLLSMIRTIFRMRSKTD 166The amino acid sequence of SEQ IDMAGAGEGTPEVTLETSMGPITVELYHKHAPKTCRNFLEL 435. The conserved cyclophilin-SRRGYYNNVKFHRVIKDFMVQGGDPTGTGRGGESIYGPR type peptidyl-prolyl cis-transFEDEITRDLKHTGAGILSMANAGPNTNGSQFFISLAPTP isomerase signature isunderlined WLDEKHTIFGRVCKGMDVVKRLGNVQTDKNDRPIHDVKI and thecyclophilin-type peptidyl- LRTTVKD prolyl cis-trans isomerase signatureis in bold. 167 The amino acid sequence of SEQ IDMMDPELMRLAQEQMSKISPDELMKMQRQIMANPDLMRMA 436. The conserved TPR repeatSENMKNLKPEDIRFAAEQMKNVRKEEMAEISERISRASP domain is underlined.EEIEAMKARANLQSAYQLQVAQNLKDQGNQLHARMKYSEAAEKYLQARNNLTGIPFSEAKSLLLASSSNLMSCYLKTGQYEECVQTGSEVLAYDAMNVKALYRRGQAYKQIGKLELAVADLRKAVEVSPEDETIAQALREASTELMEKGGTQDQNGPRIEEIIEEEAVQPTAEKYPQSAPMVTSVTEDVSDDEQGSEDQNGFSRDSFQATNAPDGQMYAESLRNLTENPDMLRTMQSLMKNVDPDSLVALSGGKLSPDMVKTVSGMFGRMSPEEIQNMMKMSSTLSRQNPSTSSRFDDITRGHSNMDSSPQSVSVDNDLFEENQNRVGESSTNLSSSAAFSGMPNFSAEMQEQVRNQMNDPATRQMFTSMIQNMSPEMMASMSEQFGVKLSPEDAVKAQNAMASLSPNDLDRLMNWATRLQTAIDYARK IKNWILGRPGLIFAISMLLLAIILHRFGYIGD168 The amino acid sequence of SEQ IDMGVEKEILRPGNGPKPRPGQSVTVHCTGYGKNEDLSQKF 437. The conserved FKBP-typeWSTKDPGQKPFTFTIGQGRVIKGWDEGVLDMQLGEIFKL peptidylprolyl isomerase domainis RCSPDYGYGSNGFPAWGIRPNSVLVFEIEVLSVN underlined and the Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature is in bold. 169 Theamino acid sequence of SEQ ID MPNPRCYLDITIGEELEGRILVELYSDVVPKTAENFRAL438. The conserved cyclophilin- CTGEKGIGPHTGVPLHYKGLPFHRVIKGFMIQGGDISAQtype peptidyl-prolyl cis-trans NGTGGESIYGLKFDDENFQLKHERRGMLSMANSGPNTNGisomerase family domain is SQFFITTTRTSHLDGKHVVFGKVIKGMGVVRGIEHTPTEunderlined and the cyclophilin- SNDRPSLDVVISDCGEIPEGSDDGIANFFKDGDLYPDWPtype peptidyl-prolyl cis-trans ADLDEKSAEISWWMNAVDSAKCFGNENYKKGDYKMALRKisomerase signature is in bold. YRKALRYLDICWEKEEIDEEKSNHLRKTKSQIFTNSSACKLKLGDLKGALLDTEFAMRDGEDNVKALFRQGQAYMALKDVDSAVASFKKALQLEPNDAGIRKELAVATKMINDRRDQ ERRAYARMFQ 170 The amino acidsequence of SEQ ID MGDVIDLNGDGGVLKTIIRSAKPGAMQPTEDLPNVDVHY 439. Theconserved FKBP-type EGTLADTGEVFDTTREDNTLFSFELGKGTVIKAWDIAVKpeptidylprolyl isomerase domain isTMKVGEVARITCKPEYAYGSAGSPPDIPENATLIFEVEL underlined and the Cyclophilin-VACKPRKGSTFGSVSDEKARLEELKKQREIAAASKEEEK type peptidyl-prolyl cis-transKRREEAKATAAARVQAKLEAKKGQGRGKGKSKGK isomerase signature is in bold. 171The amino acid sequence of SEQ IDMGLGLKIASASFLPIFNIMATRSLCILLVCFIPVLAHVL 440. The conserved cyclophilin-SLQDPELGTVRVYFQTTYGDIEFGFFPHVAPKTVEHIYK type peptidyl-prolyl cis-transLVRLGCYNSNHFFRVDKGFVAQVADVVGGREVPLNSEQR isomerase signature isunderlined. KEGEKTIVGEFSEVKHVRGILSMGRYSDPDSASSSFSILLGNAPHLDGQYAVFGKVTKGDDTLKRLEEVPTRQEGIFVMPLERIRILSTYYYDTNERESNLTCDHEVSILKRRLVES AYEIEYQRRKCLP 172 The amino acidsequence of SEQ ID MASKRSLRTMNVWPTLPPLVLLLLLCFSSMSSSVVAKKS 441. Theconserved FKBP-type DVSELQIGVKHKPKSCDIQAHKGDRIKVHYRGSLTDGTVpeptidylprolyl isomerase domain isFDSSFERGDPIEFELGSGQVIKGWDQGLLGMCVGEKRKL underlined and the Cyclophilin-RIPSKLGYGAQGSPPKIPGGATLIFDTELVAVNGKGISN type peptidyl-prolyl cis-transDGDSDL isomerase signatures are in bold. 173 The amino acid sequence ofSEQ ID MSGAPAERPISYFDITIGGKPIGRIVFSLYADLVPKTAE 442. The conservedFKBP-type NFRALCTGEKGIGKSGKPLCYAGSGFHRVIKGFMCQGGD peptidylprolylisomerase domain is FTAGNGTGGESIYGEKFEDEAFPVKHTKPFLLSMANAGK underlinedand the Cyclophilin- DTNGSQFFITVSQTPHLDDKHVVFGEVIKGKSIVRAIEN typepeptidyl-prolyl cis-trans YPTASGDVPTSPIIISACGVLSPDDPSLAASEETIGDSYisomerase signatures are in bold.EDYPEDDDSDVQNPEVALDIARKIRELGNKLFKEGQIELALKKYLKSIRYLDVHPVLPDDSPPELKDSYDALLAPLLLNSALAALRTQPADAQTAVKNATRALERLELSDADKAKALYRRASAHVILKQEDEAEEDLVAASQLSPEDMAISSKLKE VKDEKKKKREKEKKAFKKMFSS 174 Theamino acid sequence of SEQ ID MASSLRSSLFSSWALDSKSVCSLFNLNPGKMGLPSISTP443. The conserved FKBP-type LNWRTCCCSHSSELLELNEGLQSSRRKTVMGLSTVIALSpeptidylprolyl isomerase domain isLVYCDEVGAVSTSKRALRSQKVPEDEYTTLPNGLKYYDL underlined.KVGSGTEAVKGSRVAVHYVAKWKGITFMTSRQGMGITGGTPYGFDVGASERGAVLKGLDLGVQGMRVGGQRILIVPPELAYGNTGIQEIPPNATLEFDVELISIKQSPFGSSVKIVEG 175 The amino acid sequence ofSEQ ID MGAIEDEEPPLKRLKVSSPGLRRGLEEEAPSLSVGSVSI 444. The conservedG-protein beta LMAKSLSLEEGETVGSKGLIRRVEFVRIITQALYSLGYQ WD-40 repeatdomains are KAGALLEEESGILLQSSNVALFRKQILDGKWDESVVTLR underlined.GIDQVEVEGNTLKAASFLILQQKFFELLDKGNIPEAMKTLRLEISPMQLNTKRVHELASCIVFPSRCEELGYSKQGNPKSSQRMKVLQEIQQLLPPSIMIPEKRLERLVEQALNVQREACIFHNSLDPALSLYTDHQCGRDQIPTTTLQVLESHKNEVWFLQFSNNGKYLASASKDCSAIIWEITEGDSFSMKHRLSAHQKPVSFVAWSPDDKLLLTCGIEEVVKLWNVETGECKLTYDKANSGFTSCGWFPDGERFISGGVDKCIYIWDLEGKELDSWKGQGMPKISDLAVTSDGKEIISICGDNAIVMYNLDTKTERLIEEESGITSLCVSKDSRFLLLNLANQEIHLWDIGARSKLLLKYKSHRQSRYVIRSCFSSSDLAFVVSGSEDSQVYIWHRGNGELLAVLPGHSGTVNCVSWNPVNPHVFASASDDYTIRIWGVNRNTFRSKNASSSNGVVHLANGGP 176 The amino acid sequence of SEQID MPGTTAGAGIEPTEPQSLKKLSLKSLKRSFDLFASLHGE 445. The conserved G-proteinbeta PQPPDQRSQRIRIACKVRAEYEVVKNLPTLPQREVGSSV WD-40 repeat domains areSNSNVGETHSSLTTNQAQGFPTDTSGDLSKDEGKEITSI underlined and the Trp-Asp (WD)AVHLQPQTGLIDGKAGAIAGTSTAISSVGSSDRYQPSAA repeats signature is in bold.IMKRLPSKWPRPIWHPPWKNYRVISGHLGWVRSVAFDPGNEWFCTGSADRTIKIWEVATGKLKLTLTGHIEQIRGLAVSSRHPYLFSAGDDKQVKCWDLEYNKAIRSYHGHLSGVYCLALHPTLDILCTGGRDSVCRVWDIRTKAQIFALSGHENT VCSVFTQAIDPQVVTGSHDTTIKLWDLAAGKTMSTLTYH KKSVRAIAKHPFEHTFASASADNIKKFKLPKGEFLHNMLSQQKTIVNAMAINEDNVLVSAGDNGSLWFWDWKSGHNFQQAQTIVQPGSLDSEAGIYALQYDITGSRLVSCEADKTIK MWKEDETATPESHPINFKAPKDIRRF 177The amino acid sequence of SEQ IDMRPILMKGHERPLTFLKYNRDGDLLFSCAKDHTPTVWYG 446. The conserved G-proteinbeta HNGERLGTYRGHNGAVWCCDVSRDSTRLITSSADQTAKL WD-40 repeat domains areWNVETGAQLFSFNFESPARAVDLAIGDKLVVITTDPFME underlined.LPSAIHIKRIEKDLSKQTADSVLTITGIKGRINRAVWGPLNSTIISGGEDSVVRIWDSETGKLLRESDKETGHQKPITSLCKSADGSHFLTGSLDKSARLWDIRTLTLIKTYVTERPVNAVAISPLLDHVVIGGGQEASHVTTTDREAGKFEAKFFHKILEEEIGGVKGHFGPINSLAFNPDGRSFASGGEDGYV RLHHFDPDYFHIKM 178 The aminoacid sequence of SEQ ID MRPILMKGHERPLTFLKYNRDGDLLFSCAKDHTPTVWYG 447. Theconserved G-protein beta HNGERLGTYRGHNGAVWCCDVSRDSTRLITSSADQTAKL WD-40repeat domains are WNVETGNQLFSFNFESPARAVDLAIGDKLVVITTDPFME underlined.LPSAIHIKRIEKDLSKQTADSVLTITGIKGRINRAVWGPLNSTIISGGEDSVVRIWDSETGKLLRESDKETGHQKAITSLCKSADGSHFLTGSLDKSARLWDIRTLTLIKTYVTERPVNAVAISPLLDHVVIGGGQEASHVTTTDRRAGKFEAKFFHKILEEEIGGVKGHFGPINSLAFNPDGRSFASGGEDGYV RLHHFDPDYFHIKM 179 The aminoacid sequence of SEQ ID MAENNVGDFIPLDRQEYPSKPAPGAVDSSFWKSFKKKEV 448. Theconserved G-protein beta SRQIAGVTCINFCPEPPHDFAVTSSTRVHIYDGKSCELK WD-40repeat domains are KTITKFKDVAYSGVFRSDGQIIAAGGETGVIQVFNAKSQ underlined.MVLRQLKGHGRPVRVVRYSPQDKLHLLSGGDDSMVKWWDITTQEELLNLEGHKDYVRCGAASPSSVNLWATGSYDHTVRLWDLRNSKTVLQLKHGKPLEDVLFFPSGGLLATAGGNVVKVWDILGGGRPIHTMETHQKTVMAMCISKVPRSGQALGDAPSRLVTASLDGYMKVFDLDHFKVTHSARYPAPILSMGISSLCRTMAVGTSSGLLFIRQRKGQIEDKIHSDSSGLQVNPVNDEKDSAVLKPNQYRYYLRGRSEKPSEGDYVVKRMAKVYFQEYDKDLRHFNHSKALVSALKAADSKGTVAVIEELVARKRLIQTLSILNLDELELLINFLSRFILVPKYSRFLISLTDRVLDARAVDLGKSENLKKQIADLKGIVVQELRVQQ SMQELQGIIEPLIRASAR 180 The aminoacid sequence of SEQ ID MDVETSSKPTGNKRTYTRLPRQVCVFWQEGRCTRESCNF 449. Theconserved C-x8-C-x5-C-x3- LHVDEPGSVKRGGATNGFAPKRSYNGSDERDTLAAGPPG H typezinc finger is underlined GSRRNISARWGRGRGGIFISDERQKI RNKV

NYWLAGN

and in italics and the conserved QRGEE

KYL

SF VMGSDVKFLTQLSGHVKAIRGIAFPSD Cys and His residues in bold, TheSGKLYSGGQDKKVIVWDCQTGQGTDIPLNDEVGCLMSEG conserved G-protein beta WD-40PWIFVGLPNAVKAWNILTSTELSLVGPRGQVHALAVGNG repeat domains are underlinedand MLFAGTHDGSILAWKFSPASNTFEPAASLVGHTQAVVSL the Trp-Asp (WD) repeatssignature VSGADRLYSGSMDKTIRVW DL GTFQCLQTLRDHTSVVMS is in bold(non-italics). LLCWDQFLLSCSLDNTVKVWVATSSGALEVTYTHNEEHGVLALCGMNDEQAKPVLLCSCNDNTVRLYDLPSFSERGRIFSRNEVRTFQIAPGGLFFTGDATGELKVWNWATQKS 181 The amino acid sequence of SEQID MSVQELRERHAAATAKVNALRERIKAKRLQLLDTDVATY 450. The conserved G-proteinbeta ASSNGRTPISFSFTDLVCCRTLQGHTGKVYSLDWTSEKN WD-40 repeat domains areRIVSASQDGRLIVWNALTSQKTHAIKLPCAWVMTCAFSP underlined.SGQAVACGGLDSVCSIFQLNNQLDRDGHLPVSRILSGHRSYVSSCQYVPDGDTHVITGSGDRTCIQWDVTTGQRIAIFGGEFPLGHTADVMSVSISAANPKEFVSGSCDTTTRLWDTRIASRAIRTFHGHEADVNTVKFFPDGLRFGSGSDDGTCRLFDIRTGHQLQVYRQPPRENQSPTVTAIAFSFSGRLLFAGYSNGDCFVWDTILEKVVLNLGELQNTHNGRISCLGLSA DGSALCTGSWDKNLKIWAFGGHRKIV 182The amino acid sequence of SEQ IDMKVKIISRSTDEFTRERSNDLQRVFRNFDPNLHTQARAQ 451. The conserved G-proteinbeta EYVRALNAAKLDKIFAKPFLAAMSGHIDGISAMAKSPRH WD-40 repeat domains areLKSIFSGSVDGDIRLWDIAARRTVQQFPGHRGAVRGLTV underlined.STEGGRLISCGDDCTVRLWDIPVAGIGESSYGSENVQKPLATYVGKNSFRAVDYQWDSNVFATGGAQVDIWDHDRSEPTNSFAWGSDTVISVRFNPAEKDIFATTASDRSIVLYDLRMASPLNKLIMQTRNNAIAWNPREPMNFTAANEDCNCYSYDMRRMNISTCVHQDHVSAVMDIDYSPSGREFVTGSYDRTVRIFPYNAGHSREIYHTKRMQRVFCVKFSGDATYVVSGSDDANIRLWKAKASEQLGVLLPRERKRHEYLDAVKERFKHLPEIKRIERHRHLPKPIYKAALLRHTVNAAAKRKEERKR AHSAPGSVVTNPLRKKRIVAQLE 183 Theamino acid sequence of SEQ ID MDHYYQDDFDYLVDDEMVDFADDVEDDVRTRRRSDIDSD452. The conserved G-protein betaSENDFDLNNKSPDTTALQAKRGKDIQGIPWNRLNFTREK WD-40 repeat domains areYRETRLQQYKNYENLPRPRRSRNLDKECTNFERGSSFYD underlined.FRHNTRSVKATIVHFQLRNLVWATSKHNVYLMQNYSIMHWSSLKQKGEEVLNVAGPIVPSVKHPGSSPQGLTRVQVSAMSVKDNLVVAGGFQGELICKYLDKPGVSFCTKISHDENGITNAVEIYNDASGATRLMTANNDLAVRVFDTEKFTVLERFSFPWSVNHTSVSPDGKLVAVLGDNADCLLADCKTGKTVGTLRGHLDYSFAAAWHPDGYILATGNQDTTCRLWDVRKLSSSLAVLKGRMGAIRSIRFSSDGRFMAMAEPADFVHLYDTRQNYTKSQEIDLFGEIAGISFSPDTEAFFVGVADRTYG SLLEFNRRRMNYYLDSIL 184 The aminoacid sequence of SEQ ID MAEALVLRGTMEGHTDAVTAIATPIDNSDMIVSSSRDKS 453. Theconserved G-protein beta ILLWN LTKEPEKYGVPRRRLTGHSHFVQDVVISSDGQFA WD-40repeat domains are LSGSWDSELRLWDLNTGLTTRRFVGHTKDVLSVAFSIDN underlinedand the Trp-Asp (WD) RQIVSASRDRTIKLWN T LGECKYTIQPDAEGHSNWISCV repeatssignatures are in bold. RFSPSATNPTIVSCSWDRTVKVWN LTNCKLRNTLVGHGGYVNTAAVSPDGSLCASGGKDGVTMLWDLAEGKRLYSLDAGDIIYALCFSPNRYWLCAATQQCVKIWDLESKSIVADLRPDFIPNKKAQIPYCTSLSWSADGSTLFSGYTDGKIRVWG IGHV 185 The amino acid sequenceof SEQ ID MAAIKSTSRSASVAFAPDAPLLAAGTMAGAIDLSFSSLA 454. The conservedG-protein beta NLEIFKLDFQSDDPELPVVGECPSNERLNRLSWGSAGGS WD-40 repeatdomains are FGIIAGGLVDGTINIWNPATLINSEDNGDALIARLEQHT underlined.GPVRGLEFNTISTNLLASGAEDGELCIWDLANPTAPTHFPPLKGVGSGAQGEISFLAWNRKVQHILASTSYSGTTVVWDLRRQKPIISFPDATRRRCSVLQWNPDASTQLIVASDDDNSPTLEAWDLRNTISPYKEFVGHSRGVIAMSWCPSDSLFLLTCAKDNRTLCWDTGSGEIVCELPAGANWNFDVQWSPKIPGILSTSSFDGKIGIHNIEACSRNVSGEVEFGGAIVRGGPSALLKAPKWLERPAGVSFGFGGKLASFRPSTVAQAADHRHSEVFIHNLVTEDNLVIRSTEFEAAIADGEKVSLRALCDRKAEESQSDEEKETWNFLRVMFEDEGTARTKLLEHLGFKVQSEENGDLQETHSSKIDDIGSEIGKTLTLDDKTEEDVLPQLKGGQDAAIPQDNGEDFFDNLHSPKEEVSLSHVGNDFVGEKDKDMVVNGAEIEHETEDLTEYSDWNEAIQHSLVVGDYKGAVLQCLSANRMADALIIAHLGGNSLWEKTRDEYLKKAKSSYLKVVSAMVNNDLTGLVNSRPLKSWKETLAMLCTYSQREEWTVLCDMLASRLIAAGNVMAATLCYICAGNIEKTVEIWSRSLKYDYDGRSFVDHLQDVMEKTVVLALATGQKRVSPSLSKLVENYAELLASQGLLTTAMEYLKLLGTEESSHELSILRDRLYLSGTDNKVEASSFPFETRQDLTESQYNMHQTGFGAPETQKNYQENVHQVLPSGSYTDNYQPTANTHYIAGYQPAPQQQPSFQNYFTPASYQPAPSPNVFYPSQVSQAEQSNFAPPVNQPPMKTFVPSTPPILRNVDQYQTPSLNPQLYQGVSSATVETHPYQTGAPASVSVGTTPGQPSVVPNFMVPGPVTAPTVTPRGFMPVTTPTQHPLGSANPPVQPQ SPQSSQVQSV 186 The amino acidsequence of SEQ ID MAGAADSQLQTLSERDSTPNFKNLHTREYAAHKKKVHSV 455. Theconserved G-protein beta AWNCTGTKLASGSVDQTARVWNIEPHGHSKTKDLELKGH WD-40repeat domains are ADSVDQLCWDPKHSELLATASGDRTVRLWD ARSGKCSQQ underlinedand the Trp-Asp (WD) VELSGENINITFKPDGTHIAVGNRDDELTIIDVRKFKPL repeatssignature is in bold. HKRKFSYEVNEIAWNTTGELFFLTTGNGTVEVLSYPSLQVLHTLVAHTAGCYCIAIDPIGRYFAVGSADALVSLWDLSEMLCVRTFTKLEWPVRTISFNHDGQYIASASEDLFIDIADVQTGRTVHQISCRAAMNSVEWNPKYNLLAFAGDDKNKY MQDEGVFRVFGFETP 187 The aminoacid sequence of SEQ ID MAATSPVGAGSGRELANPPTDGISNLRFSNHSDHLLVSS 456. Theconserved G-protein beta WDRKVRLYDASANSLKGQFVHGGPVLDCCFHDDASGFSG WD-40repeat domains are SADNTVRRYDFSTRKEDILGRHEAPVRCVEYSYAAGQVI underlined.TGSWDKTLKCWDPRGASGQEKTLVGTYSQLERVYSMSLVGHRLVVATAGRHINVYDLRNMSQPEQRRESSLKYQTRCVRCYPNGTGFALSSVEGRVAMEFFDLSEAGQAKKYAFKCHRKSEAGRDTVYPVNAIAFHPIYGTFATGGCDGYVNVWDGNNKKRLYQYSKYPTSIAALSFSRDGRLLAVASSYTFEEG EKPHEPDAVFVRSVNEAEVKPKPKVYAAPP188 The amino acid sequence of SEQ IDMASDDEEGFKNEEAPGVVDEAEVQEGLRACFPLSFGKQE 457. The conserved G-proteinbeta KKQAPLESIHSATKRPEDPRPRRQLGPPRPPPSILAEQE WD-40 repeat domains areDSDRFVGPPRPPQFVRDDNDDGEAEIMIGPPRPPAQYSD underlined and the Trp-Asp (WD)DHDNEETIGPPKPSYLEKGEETDQMVGPSKRGSDDETSG repeats signature is in bold.DSDDGDDAVDFRVPLSNEIVLRGHTKVVSALAIDQTGSRVLTGSYDYSVRMYDFQGMTSQLKSFRQLEPAEGHQVRSLSWSPTSDRFLCVTGSAQAKIFDRDGLTLGEFVKGDMYLRDLKNTKGHISGLTCGEWHPKEKQTILTCSEDGSLRIWD VNDFNTQKQVIKPKLAKPGRVPVTACAWGRDGKCIAGGVGDGSIQVWNLKPGWGSRPDLYVAKGHDDDITGLQFSADGNILLTRSTDETLKVWDLRKAITPLQVFRDLPNNYAQTNVAFSPDERLIFTGTSVERDGNSGGLLCFYDRQTLELVLRIGVSPVHSVVRCTWHPRHNQVFATVGDKKEGGAHILYDPALSERGALVCVARAPRKKSLDDFEAKPVIHNPHALPLFRDEPSRKRQREKARMDPMKSQRPDLPVTGPGFGGRVGSTKGSLLTQYLLKEGGLIKETWMEEDPREAILKYADVAAKDPKF IAPAYAQTQPETVFAETDSEEEQK 189 Theamino acid sequence of SEQ ID MKERGQSHAGQPSVDERYTQWKSLVPVLYDWLANHNLVW458. The conserved G-protein betaPSLSCRWGPQMHQATYKNSQRLYLSEQTDGTVPNTLVIA WD-40 repeat domains areTCEVVKPRVAAAEHISQFNEEARSPFVKKFKTIIHPGEV underlined.NRIRELPQNSKIVATHTDGPDVLIWDVDTQPNRQATLGAADSRPDLVLTGHKDNAEFALAMSPSAPFVLSGGKDKCVLLWSIQDHISAATEPSSAKASKTPSSAHGEKVPKIPSIGPRGVYKGHKDTVEDVQFCPSNAQEFCSVGDDSALILWDARNGNEPVIKVEKAHNADLHCVDWNPHDENLILTGSADNSVRMFDRRNLTSSGVGSPVHKFEGHSAPVLCVQWCPDKASVFGSAAEDSYLNVWDYEKVGKNVGKKTPPGLFFQHAGHRDKVVDFHWNSFDPWTIVSVSDDGESTGGGGTLQIWRMSDL IYRPEDEVLAELERFEAHILSCQNK 190The amino acid sequence of SEQ ID MSSLSRELVFLILQFLDEEKFKESVHKLEQESG

NMK 459. The conserved G-protein betaYFDEKAQAGEWDEVERYLSGFTKVDDNRYSMKIFFEIRK WD-40 repeat domains areQKYLEALDRQDRAKAVDILVKDLKVFSTFNEELYKEITQ underlined. The LissencephalyLLTLDNFRENEQLSKYGDTKSARTIMMSELKKLIEANPL type-1-like homology motif is inFREKLIYPNLKASRLRTLINQSLNWQHQLCKNPRPNPDI bold and the CTLH, C-terminal toKTLFTDHACGPPNGARTPTQPTASLGVLPKATTFTPIGP LisH motif is in italics.HGPFPSSSTATSGLASWMSNPNMVTSPQAPVAVGPSVPVPPNQATLLKRPRTPPGSSSVVDYQTADSEQLIKRLRPVSQSIDEATYPGPTLRVPWSTDDLPKTLARALNEPYPVTSIDFHPSQQTFLLVGTKNGEITLWEVGSREKLATRSFKIWDNANCSNHLEAAFVKDSSVSINRVLWSPDGTLIGIAFTKHLVHTYTFQGLDLRQHLEIDAHVGGVNDLAFSHPNKQLCVVTCGDDKMIKVWDAVTGRKLYNFEGHDAPVYSVCPHHKENIQFIFSTAVDGKIKAWLYDHLGSRVDYDAPGHSCTTMMYSADGTRLFSCGTSKEGESFLVEWNESEGAIKRTYSGLRKKGSGVVQFDTTQNHFLAVGDEHLIKFWDMDSTNMLTSCDAEGGLLNLPRLRFNKEGSLLAVTTVNGIKILANADGQKLLKTMENRTFDLPSRAHIDAASATSSPATGRMERIERTSSANTVSGINGVDPAQSSEKLRLSDDLSEKTKIWKLTEITDSIQCRCITLPENAAEPASKVSRLLYTNSGVGLLALGSNAVHKLWKWNRSEQNPSGKATASVHPQRWQPTSGLLMTNDITDINPEEAVPCIALSKNDSYVMSASGGKVSLFNMMTFKVMTTFMPPPPASTFLAFHPQDNNIIAIGMEDSTIHIYNVRVDEVKTKLKGHQKRITGLAFSSTQNILVSSGADAQLCVWNTETWEKRKSKTIQMPVGKTVSGDTRVQFHSDQLHILVVHETQLAIYDAYKLERQYQWVPQDALSAPILYATYSCNR QLIYATFSDG 191 The amino acidsequence of SEQ ID MAKDEEEFRGEMEERLVNEEYKIWKKNTPFLYDLVITHA 460. Theconserved G-protein beta LEWPSLTVQWLPDREEPPGKDYSVQKMILGTHTSDNEPN WD-40repeat domains are YLMLAQVQLPLEDAENDARQYDDERGEIGGFGCANGKVQ underlined.VIQQINHDGEVNRARYMPQNPFIIATKTVSAEVYVFDYSKHPSKPPQDGGCHPDLRLRGHNTEGYGLSWSPFKHGHLLSGSDDAQICLWDINVPAKNKVLEAQQIFKVHEGVVEDVAWHLRHEYLFGSVGDDRHLLIWDLRTSATNKPLHSVVAHQGEVNCLAFNPFNEWVLATGSADRTVKLFDLRKISSALHTFSCHKEEVFQIGWSPKNETILASCSADRRLMVWDLSRIDEFQTPEDALDGPPELLFIHGGHTSKISDFSWNPCEDWVI ASVAEDNILQIWQMAENIYHDEEDDMPPEEVV192 The amino acid sequence of SEQ IDMSPGVKQTGSQKFESGHQDVVHDVTMDYYGKRIATCSAD 461. The conserved G-proteinbeta RTIKLFGLNASDTPSLLASLTGHEGPVWQVAWAHPKFGS WD-40 repeat domains areMLASCSYDGRVIIWREGQQENEWSQVQVFKEHEASVNSI underlined.SWAPHELGLCLACGSSDGSITVFTCREDGSWDKTKIDQAHQVGVTAVSWAPASAPGSLVGQPSDPIQKLVSGGCDNTAKVWKFYNGSWKLDCFPPLQMHTDWVRDVAWAPNLGLPKSTIASCSQDGKVVIWTQGKEGDKWEGRILNDFKIPVWRVNWSLTGNILAVADGNNSVTLWKEAVDGDWNQVTTVQ 193 The amino acid sequence of SEQID MSSGVKQTGSQKFESGHQDVVHDVTMDYYGKRIATCSAD 462. The conserved G-proteinbeta RTIKLFGMNTSDTPTLLASLTGHEGPVWQVAWAHPKFGS WD-40 repeat domains areMLASCSYDRRVIIWREGQQENEWSQVQVFKEHEASVNSI underlined.SWAPHELGLCLACGSSDGSITVFTGREDGSWDKTKIDQAHQVGVTAVSWAPASAPGSLVGQPSDPVQKLVSGGCDNTAKVWKFYNGSWKLDCFPPLQMHTDWVRDVAWAPNLGLPKSTIASCSQDGRVVIWTQGKEGDKWEGKILNDFKTPVWRISWSLTGNILAVADGNNNVTLWKEAVDGEWNQVTTVQ 194 The amino acid sequence of SEQID MKKRSRPSNGHLSTAAKNKSRKTAPITKDPFFDSAHNRN 463. The conserved G-proteinbeta KSKGKGKSRGKGEEIFSSDEDDDAIGRDAPAEEEEEIAE WD-40 repeat domains areEERETADEKRLRVAKAYLDKIRAITKANEEDNEEEAGED underlined.EETEAERRGKRDSLVAEILQQEQLEESGRVQRQLASRVVTPSKLVECRVVKRHKQSVTAVALTEDDLRGFSASKDGTIIHWDVETGASEKYEWPSQAVSVSSSNEVSKTQKSKGSKKQGSKHVLSMAVSSDGRYLATGGLDRYIHLWDTRTQKHIQAFRGHRGAVSCLAFRQGTQQLISGSFDRTIKLWSAEDRAYMDTLYGHQSEILAVDCLRKERVLSVGRDHTLRLWKVPEETQLVFRGHAASLECCCFINNEDFLSGSDDGSIELWSMLRKKPVFMAKNAHGHAIVENLSEDTSTREEPDEEVTTRQLPNGNSIGNGMTNQMGITPSVESWVGAVTVCRGTDLAASGAGNGVVRLWAIENSSKSLRALHDIPLTGFVNSLTFARSGRFLIAGVGQEPRLGRWGRIQAARNGVTLCPIELS 195 The amino acid sequence of SEQ IDMAATFGTINTATSPHNPNKSFEIVQPPNDSISSLSFSPK 464. The conserved G-proteinbeta ANYLVATSWDNQVRCWEVLQTGASMPKAAMSHDQPVLCS WD-40 repeat domains areTWKDDGTAVFSAGCDKQAKMWPLLTGGQPVTVAMHDAPI underlined.KDIAWIPEMNLLATGSWDKTLKYWDTRQSNPVHTQQLPERCFALSVRHPLMVVGTADRNLIIFNLQNPQTEFKRISSPLKYQTRCVAAFPDKQGFLVGSIEGRVGVHHVEEAQQSKNFTFKCHRDSNDIYAVNSLNFHPVHQTFATAGSDGAFNFWDKDSKQRLKAMARSNQPIPCSTFNSDGSLYAYAVSYDWSKGAENHNPATAKHHILLHVPQESEIKGKPRVTTSGRK 196 The amino acid sequence of SEQID MVVMDKGTHQTNEDESESEFIDEDDVIDEISIDEEDLPD 465. The conserved G-proteinbeta ADVEGEDVQEDNKRSEPDENSSSLDDAIHTFEGHEDTLF WD-40 repeat domains areAVACSPVDATWVASGGGDDKAFMWRIGHATPFFELKGHT underlined.DSVVALSFSNDGLLLASGGLDGVVRIWDASTGNLIHVLDGPGGGIEWVRWHPKGHLVLAGSEDYSTWMWNADLGKCLSVYTGHCESVTCGDFTPDGKAICTGSADGSLRVWNPQTQESKLTVKGYPYHTEGLTCLSISSDSTLVVSGSTDGSVHVVNIKNGKVVASLVGHSGSIECVRFSPSLTWVATGGMDKKLMIWELQSSSLRCTCQHEEGVMRLSWSLSSQHIITSSLDGIVRLWDSRSGVCERVFEGHNDSIQDMVVTVDQRFILTGS DDTTAKVFEIGAF 197 The amino acidsequence of SEQ ID MPVFRTAFNGYAVKFSPFVETRLAVATAQNFGIIGNGRQ 466. Theconserved G-protein beta HVLELTPNGIVEVCAFDSSDGLYDCTWSEANENLVVSAS WD-40repeat domains are GDGSVKIWD IALPPVANPIRSLEEHAREVYSVDWNLVRK underlinedand the Trp-Asp (WD) DCFLSASWDDTIRLWTIDRPQSMRLFKEHTYCIYAAVWN repeatssignature is in bold. PRHADVFASASGDCTVRIWDVREPNATIIIPAHEHEILSCDWNKYNDCMLVTGSVDKLIKVWDIRTYRTPMTVLEGHTYAIRRVKFSPHQESLIASCSYDMTTCMWDYRAPEDALLARYDHHTEFAVGIDISVLVEGLLASTGWDETVYVWQHGMD PRAC 198 The amino acid sequenceof SEQ ID MDSRNRRSRLNLPPGMSPSSLHLETTAGSPGLSRVNSSP 467. The conservedG-protein beta STPSPSRTTTYSDRFIPSRTGSRLNGFALIDKQPQPLPS WD-40 repeatdomains are PTRSAAEGRDDASSSSASAYSTLLRNELFGEDVVGPATP underlined.ATPEKSTGLYGGSRDSIKSPMSPSRNLFRFKNDHGGNSPGSPYSASTVGSEGLFSSNVGTPPKPARKITRSPYKVLDAPALQDDFYLNLVDWSSNNVLAVGLGTCVYLWSACTSKVTKLCDLGVNDSVCSVGWTPQGTHLAVGTNIGEVQIWDTSRCKKVRTMGGHCTRAGALAWSSYILSSGSRDRNILHRDIRVQDDFIRKLVGHKSEVCGLKWSYDDRELASGGNDNQLLVWNQQSAQPLLRFNEHTAAVKAIAWSPHQHGILASGGGTADRCLRFWNTATDTRLNCVDTGSQVCNLVWCKNVNELVSTHGYSQNQIMVWRYPSMSKLATLTGHTLRVLYLAISPDGQTIVTGAGDETLRFWSIFPSPKSQSAVHDSGLWSLGRTHIR 199 The amino acid Sequence ofSEQ ID MEKKKVVVPIVCHGHSRPIVDLFYSPVTPDGLFLISASK 468. The ConservedG-protein beta DSSTMLRNGETGDWIGTFEGHKGAVWSCCLDNRALRAAS WD-40 repeatdomains are GSADFSAKIWDALTGDELHCFVHKHIVRACAFSESTSLL underlined.LTGGHEKILRIFDLNRPDAPPKEVDNSPGSIRTVAWLHSDQTILSSNSDAGGVRLWDLRTEKIVRVLETKSPVTSAEVSQDGRYITTADGNSVKFWDANHFGMVKSYTMPCMVESASLEPTMGNMFVAGGEDMWVRLFDFHTGEEIACNKGHHGPVHCVRFAPGGESYSSGSEDGTIRIWQTLNMNSEENESYGVNGLSGKVRVGVDDVVQKVEGFQITADGHLNDKPEKPNP 200 The amino acid Sequence ofSEQ ID MERYSQGTQKKSEIYTYEAPWQIYGMNWSVRKDKKFRLG 469. The ConservedG-protein beta IGSFLEEYNNRVEIIELDEESGEFKSDPRLAFDHPYPTT WD-40 repeatdomains are KIMFVPDKECQRPDLLATTGDYLRIWQVCEDRVEPKSLL underlined.NNNKNSEFCAPLTSFDWNDADPKRIGTSSIDTTCTIWDIEKEVVDTQLIAHDKEVYDIAWGEVGVFASVSADGSVRVFDLRDKEHSTIIYESSQPETPLLRLGWNKQDPRFIATILMDSCKVVILDIRFPTLPVAELQRHQASVNTIAWAPHSPCHICTAGDDSQALIWELSSVSQPLVEGGGLDPILAYTAAAE INQLQWSSMQPDWVAIAFSNEVQILRV 201The amino acid sequence of SEQ IDMQSENNLDESLHLREVQELQGHTDTVWAVAWNPVTGIDG 470. The conserved G-proteinbeta APSMLASCSGDKTVRIWENTHTLNSTSPSWACKAVLEET WD-40 repeat domains areHTRTVRSCAWSPNGKLLATASFDATTAIWENVGGEFECI underlined.ASLEGHENEVKSVSWSASGMLLATCGRDKSVWIWDVQPGNEFECVSVLQGHTQDVKMVQWHPNRDILVSASYDNSIKVWAEDGDGDDWACMQTLGNSVSGHTSTVWAVSFNSSGDRMVSCSDDLTLMVWDTSINPAERSGNAGPWKHLCTISGYHD RTIFSVHWSRSGLIASGASDDCIRLFS 202The amino acid sequence of SEQ IDMKRAYKLQEFVAHASNVNCLKIGKKSSRVLVTGGEDHKV 471. The conserved G-proteinbeta NMWAIGKPNAILSLSGHSSAVESVTFDSAEALVVAGAAS WD-40 repeat domains areGTIKLWDLEEAKIVRTLTGHRSNCISVDFHPFGEFFASG underlined and the Trp-Asp (WD)SLDTNLKIWDIRRKGCIHTYKGHTRGVNSIRFSPDGRWV repeats signature is in bold.VSGGEDNIVKLWDLTAGKLMHDFKCHEGQIQCMDFHPQE FLLATGSADRTVKFWDLETFELIGSAGPETTGVRAMIFN PDGRTLLTGLHESLKVFSWEPLRCYDAVDVGWSKLADLNIHEGKLLGCSYNQSCVGVWVVDISRVGPYAAGNVSRTNGHNEAKLASSGHPSVQQLDNNLKTNMARLSLSHSTESGIKEPKTTTSLTTTEGLSSTPQRAGIAFSSKNLPASSGPPSYVSTPKKNSTSRVQPTTNFQTLSRPDIVPVIVPRSNSLRPETTSDVKKEMNNFGRVVPSTVSTKSTDVIKSGSNRDESDKIDSINQKRMTGNDKTDLNIARAEQHVSSRLDNTNTSSVVCDGNQPAARWIGAAKFRRNSPVDPVVSPHDRSPTFPWSATDDGVTCQPDRQVTAPELSKRVVEPGRARALVASWETREKALTADTPVLVSGRPPTSPGVDMNSFIPRGSHGTSESDLTVSDDNSAIEELMQQHNAFTSILQARLTKLQVIRRFWQRNDLKGAIDATGKMGDHSVSADVISVLIERSEIFTLDICTVILPLLTRLLQSETDRHLTVAMETLLVLVKTFGDVIRATISATPTIGVDLQAEQRLERCNLCYVELENIKQILVPLI RRGGAVAKSAQELSLALQEV 203 Theamino acid sequence of SEQ ID MSTLEIEARDVIKIVLQFCKENSLHQTFQTLQNECQVSL472. The conserved G-protein betaNTVDSLETFVADINSGRWDVILPQVAQLKLPRKKLEDLY WD-40 repeat domains areEQIVLEMIELRELDTARAILRQTQAMGFMKQEQPERYLR underlined and the Trp-Asp (WD)LEHLLVRTYFDPREAYHESSKEKRRSQIAQALASEVTVV repeats signature is in bold.PPSRLMALIGQSLKWQQHQGLLPPGTQFDLFRGTAAVKADEEEMYPTTLAHTIKFGKQSHPECARFSPDGQYLVSCSVDGFIEVWDYISGKLKKDLQYQADDSFMMHDDAVLCVDFSRDSEMLASGSQDGKIKVWRIRTGQCLRRLERAHSQGVTSLSFSRDGSQLLSTSFDSTARIHGLKSGKALKEFRGHTSY VNDAIFTSDGGRVITASSDCTVKVWDVKTTDCIQTFKPP PPLKGGDVSVNSVHLFPKNSEHIVVCNKASSIYIMTLQGQVVKSFSSGKREGGDFVAACISPKGEWIYCVGEDRNIYCFSQQSGKLEHLMKAHDKDIIGVTPHPHRNLLVTYSEDST MKIWKP 204 The amino acidsequence of SEQ ID MDIELEDQPFDLDFHPSAPIVAVALITGRLQLFRYVDIS 473. Theconserved G-protein beta SEPERLWTVTAHTESCRAARFINAGSSVLTASPDCSILA WD-40repeat domains are TNVETGQPVARLDNAHGAAINCLTNLTESTIASGDENGI underlined.IKVWDTRQNSCCNKFKAHEDYISDMEFVPDTMQLLGTSGDGTLSVCNLRKNKVHARSEFSEDELLSVALMKNGKKVVCGSQEGVLLLYSWGYFKDCSDRFVGHPHSVDALLKLDEDTVLTGSSDGIIRVVSILPNKMIGVIGEHSSYPIERLAFSHDRNVLGSASHDQILKLWDIHYLHEDDEPETNKQEAVNDENVDMDLDVDTEKRPRGSKRKKRAEKGQTSSQKQSSDFFA DI 205 The amino acid sequenceof SEQ ID MDRIQQIPHTCVARKINLPLGMSKESLALNLPANLAPTM 474. The conservedG-protein beta SPPSITYSDRFIPSRKASNFEEFALPDKTSPSPNSAGGQ WD-40 repeatdomains are SSSTNGEGRDDACAAYSALLRTELFPATPDKTEGCRRPV underlined.IGSPSGNVFRFKSQQCKSQSPFSLCPVGEDGDLSETGAVARKTTRKIPRSPFKVLDAPALQDDFYLNLVDWSSHNILAVGLSACVYLWSASSSKVTKLCDLGLDDNVCSVAWTQRGTYLAVGTNNGGVQIWDAAHCKQVRTMEGHCTRVGTLAWNSHILSSGGRDRNILQRDIRAQDDFVSKFSGHKSEVCGLKWSYDNRELASGGNDNQLFVWNQQSQQPVLKYNEHTAAVKAIAWSPHQHGLLASGGGTADRCIRFWNTATNTSLNCVDTGSQVCNLVWSKNVNELVSTHGYSQNQIIVWRYPTMSKLATLTGHTLRVLYLAISPDGQTIVTGAGDETLRFWNVFPSSK TQQNTIRDMGVWSSGRTHIR 206 Theamino acid sequence of SEQ ID MAGGQGEGEEKVDKLSMELTEDVMKSMEIGAVFKDYNGK475. The conserved G-protein betaINSLDFHRTNNYLVTASDDEAIRLFDTASATWQKTSYSK WD-40 repeat domains areKYGVDLICFTNHQTSVLYSSKNGWDESLRHLSLMDNKYL underlined.RYFKGHHDRVVSLCMSPKGECFMSGSLDRTVLLWDLRIDKCQGLIRVRGRPAVAYDEQGLVFAISNEGGLIKMFDARLYDKGPFDTFVVEGDKSEASGIKFSNDGKLILLSTMDSNIHVLDAYQGTTVHSFSVEAVPNGGEAVPNGGTLEASFSPDGKFVISGSGNGNIHAWSVNSGKEVACWTTEGVIPAVVKWAPRRLMFASGSSVLSLWVPDLSKLASLTGSNSNSAY 207 The amino acid sequence of SEQID MHRVGSTGNTSNSSRPRREKRLTYVLNDANDSRHCSGIN 476. The conserved G-proteinbeta CLVISKLSLLGGNDYLFSGSRDGTLKRWELADDSAVCSA WD-40 repeat domains areTFESHVDWVNDAVLTGETLVSCSSDTTLKTWRPFSDGVC underlined.TRTLRQHSDYVTCLAAASKNSNIVASGGLGREVFIWDIEAAMAPVSRTSEAMDDDTSNGVLSSGNSVLSTTVRSTNATNSASLHTSQLQGYTPIAAKGHKESVYALAMNDVGTLLVSGGTEKVVRVWDPRSGAKQMKLRGHTDNVRALILDSTGRFCLSGSSDSIIRLWDLGQQRCVHSYAVHTDSVWALASTPNFSHVYSGGRDLSLYLTDLTTRESLLLCMEKHPLLRLTLQDDSIWVATTDSSLHRWPAEGQNPPKMFQRGGSFLAGNLSFTRARACLEGSAPVPVNTQPSFVIPGSPGIVQHEILNNRRHVLTKDAEGTVKLWEITRGAVLDDYGKVSFEEKKEELFEMVSIPAWFTMDTRLGSMSVHLDTPQCFTAEMYAVDLNVPDAPEEQKINLAQETLRGLLAHWLSRRRQRLATQASANGDFPAGQENALRNHISSRIDVHDDAETHIAGILPAFDFSTTSPPSIITEGSQGGPWRKKITDLDGTEDEKDFPWWCLECVLHGRLSPRESLKCSFYLHPYEGTTVQVLTQGKLSAPRILRIQKVINYVLEKMVLDRPLDSSNSETTFTPGLSGNQSHAAVVGDGSLRSGARVWQQKAKPLVEILCNNQVLSPDMSL ATVRTYIWKKPDDLYLYYRLVQNR 208 Theamino acid sequence of SEQ ID MMKGKTIQMQAAHQNHDGETSVACVLWDWHAKHLITAGA477. The conserved G-protein betaDNTILIHSYPSSSSSKPITLRHHKNAVTALAINSNVRSL WD-40 repeat domains areASGSVDHSVKLYSYPGGEFQSNVTRFTLPIRSLAFNKSG underlined.ELLAAAGDDEGIKLISTIDNSIARVLKGHNGPVTSISFDPKNEFLASSDSDGTVIYWELSTGKPVHTLKKIAPNTTSNPTSLNQISWRPDGEMLAVPGRKSEVSMYDRDTAEKLFSLKGGHSDTICSLAWSPNGKYIATAGTDRQVMVWDADRRQDIDKQRFDNPICSVAWKPSDNALAVIDVLGRFGVWESPIASHMKSPADGAERYDNMEDEEPLMARYEEELEDSVSGSLNEIINDDDDDDEMGKIPRKILQKKPSVKVEKGKEESNAKAFKSGQDSFKLKSAMQEAFQPGATQRQSGKRNFLAYNMLGSVITFDNDGFSHIEVDFHDIGKGCRVPSMTDYFGFTMASLSESGSVFGSPQKGEKNPSTLMYRPFSSWANNSEWSMRFPMGEEVKAVALGSGWVAAVTSLNFLRVFSEGGLQKFVLSMDGPVVTAAGYENLLVVVSHASNPLLSGDQVLSFTVYDISQKTCPLSGRLPLSPGSHLTWLGFSEEGLLSSYDSEGNLRVFTNDYNGCWVPIFSAARERKSETESIWMVGLNSTQVFCVVCKLPDTYPQVAPKPVLSVLNLSLPLACSDLGADDLENEYLRGSLLLSQMQKKAEDAVACGRESNMEEDSIFKMEAALDRCLLRLIANCCKGDKLVRATELARLLSLEKSLQGAIKLVSAMKLPMLAERFNTILEEKILQENMETISCRRLTSEAQDMDTPISISVKQVSYGANLGDSPFLPNRQVEPKHSTPVFSKPDTKIEVDTSEAIAKGCDAQNGNIKSGDAEVQPASHNDSIQKPSNPFAKASNTSANQAVQRNASLLSSIKQMKT ATENEGKRKERARSGSLPQKPAKQSKIS 209The amino acid Sequence of SEQ IDMKQKRKGHQVDDPKYSVQTPQEDDTPNESGPASEEVESS 478. The conserved G-proteinbeta DEEGGNSSNIEDDIIYSSSEEDPVVSSDYEEDEDAESDA WD-40 repeat domains areEGVTAEQELEGDIDNALQNYMGTLTVLSNFHGENLKNAE underlined.GEDTSGDDDDEEEMPKRAEESDSPEDENDERPKRAEESDFSEDEDEERPKRAEESDSSEDEVPSRNTVGDVPLRWYKDEQHIGYDIKGKKIKKQPKKDQLDSFLASTDDSSDWRKVYDEYNDEEVELTKDEIKFISRLRKGTIPHADVNPYEPYVDWFDWKDKGHPLSNAPEPKRRFIPSKWEAKKVVKLVRAIRKGWITFQKAEEKPRFYLMWGDDLKPSEKMANGLSYIPAPKPKLPGHEESYNPPPEYIPTQEEINSYQLMYEEDRPKFIPKRFDSLRNVPAYDRFLSEIFERCLDLYLCPRTRKKRINIDPESLIPKLPKPKDLQPFPSICFLEYKGHTGAVSCISPESSGQWLASGSKDGTVRIWEVETARCLKVWDIGRPIQHIAWNPVSQLSILAVAVDEEVLVLNTGLGSEDSQEKVAELLHVKSKPVSADDLGDNTSLTKWIKHEKFDGIKLTHLKPVHLISWHHKGDYFATVAPDGNTRAVLVHQLSKQQTQNPFKKMQGRVVHVLFHPSRAIFFVATKTHVRVYDLVKQQLVKRLVTGLHEVSSMAVHHKGDNLLVGSKEGKVCWFDMDLSTQPYKTLKNHSKDIHSVAFHDSYPLFASCSDDCKAYVFYGLVYSDLLQNPLIVPLKVLQGHQSVNGMGVLDCQFHPKQPWL FTAGADSVVKLYCN 210 The aminoacid sequence of SEQ ID MMSLKRGFEESLVPAKRQKTELSTVTYGDGPRRTSSLES 479. Theconserved G-protein beta PIMLLTGHHAAIYTMKFNPTGTVIASGSHEREIFLWNVH WD-40repeat domains are GDCKNFMVLKGHKNAVLDLHWTTDGCQIISASPDKTLRA underlined.WDVETGKQIKKMAEHSSFVNSCCPSRRGPPLVVSGSDDGTAKLWDLRHRGAIQTFPDKYQITAVGFSDAADKIYSGGIDNEIKVWDLRRGEVTMRLQGHTDTITGMQLSSDGSYLLTNSMDCSLRIWDMRPYAPQNRCVKILTGHQHNFEKNLLKCSWSSDGSKVTAGSADRMVYIWDTTTRRILYKLPGHTGSVNETGFHPTQPIIGSCSSDKQIYLGEIEPNVGYQAVI 211 The amino acid sequence of SEQID MEFSDTYKHTGPCCFSPDARYLAIAVDYRLVIRDVVTLK 480. The conserved G-proteinbeta VVQLYSCMDKISNIEWALDSEYILCGLYKRAMVQAWSLS WD-40 repeat domains areQPEWTCKIDEGPAGIAHARWSPDSRHIITTSDFQLRLTV underlined.WSLVNTACIHIQWPKHASKGVSETQDSKfAAIATRRDCKDYVNLLSCHTWEVMGTFTVDTIDLADLEWSPNDSAIVVWDSPLEYKVLIYSPDGRCLFKYQAYDSWLGVKTVAWSPCSQFLAVGSYDQTLRTLNHLTWKPFAEFVHVSTVRGPASAVVFKEVEEPWNLDVSGLHLNDDNAHDIQDGKPAEGHSRVRYKVVEFPVNVSSQKHPVDKPNPKQGIGLLAWSRDSQYLFTRNDNMPTALWIWDICRLELAALLIQKEPIRAAAWDPVYPRVALCTGSSHLYMWTPSGACCVNIPLPQFVVSDLKWNP DGTSMLLKDRESFCCTFVPMLPEFNDDETNEE212 The amino acid sequence of SEQ IDMAKLIETHSCVPSTERGRGILIAGDAKTNSIIYCNGRSV 481. The conserved G-proteinbeta IMRNLDNPLEASVYGEHSYPATVARFSPNGEWVASGDTS WD-40 repeat domains areGTVRIWGRGSDHTLKYEYKALAGRIDDLEWSADGQRIVV underlined.CGDSKGKSMVRAFMWDSGTNVGEFDGHSRRVLSCSFKPTRPFRVATCGEDFLVNFYEGPPFRFKTSHRDHSNYVNCVRFAPDGSKFITVGSDRKGVIFDGKMGEKIGELSKEGGHTGSIYAASWSPDSKQVLTVSADKSAKIWEISETGNGTVKKTLTFGSQGGADDMLVGCLWLNDYLITVSLGGIVSLLSAVDPDKPPKTISGHMKSINAIALSLQSGQSEVCSSSYDGVIVRWILGVGYAGRVERKDSTQIKCLATIEGELVTCGFDNKVRRVPLLSEQHKESEPIDIGAQPKDLDVAVGCPELTFVSTDAGIIIIRASKIVSTTNVGYAVTAAAISPDGTEAVVGGQDGKLRVYSIKGDTLLEESVLERHRGPINAIRFSPDGSMFASGDLNREAVVWDRITREVKLKNMVYHTARINCIAWSPDSSKVATGSLDTCILIYEVGKPASSRITIKGAHLGGVYGL AFSDQSTVISAGEDACVRVWSLP 213 Theamino acid sequence of SEQ ID MPQPSVILATAGYDHTVRFWEATSGRCYRTLQYPDSQVN482. The conserved G-protein betaHLEITPDKQYLAAAGNPHIRLFEVNSNNPQPVISYDSHT WD-40 repeat domains areNNVTAVGFQCDGKWMYSGSEDGTVKIWDLRAPGFQREYE underlined and the Trp-Asp (WD)SRAAVNTVVLHPNQTELISGDQNGNIRVWDLNANSCSCE repeats signature is in bold.LVPEDTAVRSLTVMWDGSLVVAANNHGTCYVWRLMRGTQTMTNFEPLHKLQAHNSYILKCLLSPEFCEHHRYLATTSS DQTVKIWNVDGFTLERTLTGHQRWVWDCVFSVDGAFLVT ASSDSTARLWDLSTGEAIRTYQGHHKATVCCALHDGTDGASC 214 The amino acid sequence of SEQ IDMLTKFETKSNRVKGLSFHPKRPWILASLHSGVIQLWDYR 483. The conserved G-proteinbeta MGTLIDKFDEHDGPVRGVHFHKTQPLFVSGGDDYKIKVW WD-40 repeat domains areNYKMRQCLFTFVGHLDYIRTVHFHNEYPWIVSASDDQTI underlined and the Trp-Asp (WD)RLWNWQSRVCISVLTGHNHYVMSASFHPKEDLVVSASLD repeats signature is in bold.The QTVRVWD ISGLRKKTVSPADDLSRLAQMNTDLFGGGDVV coatomer WD associatedregion is VKYVLEGHDRGVNWAAFHTSLPLIVSGADDRQVKLWRMN in bold/italics.DTKAWEVDTLRGHTNNVSCVIFHARQDIIVSNSEDKSIRVWDMSKRTSVQTFRREHDRFWILAAHPEMNLLAAGHDSG MIVFKLERERPAYVVYGGSLLYVK

IPVLPPGKKSSLLMPPAPILHGGDWPLLRVTKGIFEGGLENSTSAAYEEEDEEAAADWGEDIDIENIEGENGEATVLDDQEVKGGEDDEGGWDMEDLELPPDVAAANVGTNQKTLFVAPTLGMPVSQIWMQKSSLAGEHAAAGNFETALRLLTRQLGIKNFSPLKPLFLELYMGSHTFLPSFASVPAFSLALQRGWSESASPNIRGPPALVYRLSVLEEKLTVAYRATTEG RFSEALRLFL 215 The amino acidsequence of SEQ ID MDLLQNYQDDSEDSNPELRNHPPLEDATATSAPAGVENE 484. Theconserved G-protein beta TSSSPDSSPLRLALPAKSCAPDVDETLMALGVPGSEKKN WD-40repeat domains are NHNKPIDPTQHSVTFNPSYDQLWAPLYGPAHPYAKDGIA underlined.QGMRNHKLGFVEDSAIEPFMFDEQYNTFHRYGYAADPSASLGSHIVGDLESLKKNDGASVYNLPKREHKRQKLEKKMIQKDENEEEEKEVGEEVDNPSTEEWLKKNRKSPWAGKKEGLQTELTEEQKKYAQEHAEKKGDREKGEKVEIVDKTTFHGKEERDYQGRSWIDPPKDAKATNDHCYIPKRWVHTWSGHTKGVSAIRFFPKYGHLLLSAGMDTKVKIWDVFNSGKCMRTYMGHSKAVRDISFSNDGSRFLSAGYDRNIKLWDTETGKVISTFSTGKIPYVVKLHPDEDKQNVLLAGMSDKKIVQWDMNSGEITQEYDQHLGAVNTITFVDNNRRFVTSSDDKSLRVWEFGIPVVIKYISEPHMHSMPSISLHPNTNWLAAQSLDNQILIYSTRERFQLNKKKRFAGHIAAGYACQVNFSPDGRFVMSGDGEGRCWFWDWKTCKVFRTLKCHDNVCIGCEWHPL EQSKVATCGWDGMIKYWD 216 The aminoacid sequence of SEQ ID MARKGLGTDPAIGSLMSSKKRKEYKVTNRFQEGKRPLYA 485. Theconserved G-protein beta IAFNFIDARYHNIFATAGGTRVTIYQCLEGGAISVLQAY WD-40repeat domains are VDDDKDESFYTLSWACDVNGSPLLVAGGHNGIIRVLDVA underlinedand the Trp-Asp (WD) NEKVHKSFVGHGDSVNEIRTQALKPSLILSASKDESVRL repeatssignature is in bold. WN VQTGICILIFAGAGGHRNEVLSVDFHPSDVYRIASCGMDNTVKIWSMKEFWTYVEKSFTWTDLPSKFPTKYVQFPVFIAAVHSNYVDCTRWLGNFILSKSVDNEVVLWEPYSKEQSTSDGVVDILQKYPVPECDIWFIKFSCDFHYNSMAVGNREGKVYVWELQSSPPNLIARLSHAHCKNPIRQTAISHDGS TILCCCDDGSMWRWDVVQ 217 The aminoacid sequence of SEQ ID MESGAGGSVGARVPSAKPEMLQQPPYSNGDDDNDMERGT 486. Theconserved G-protein beta APVPSSNPNTVSKWELDKDFLCPICMQTMKDAFLTACGH WD-40repeat domains are SFCYMCIMTHLNNKSNCPCCSLYLTNNQLFPNFLLNKLL underlinedand the Trp-Asp (WD) KKTSACQMASTASPVENLCLSLQQGAEVSVKELDFLLTL repeatssignature is in bold. LAEKKRKMEQEEAETNMEILLDFLQRLRQQKQAELNEVQADLHYIKDDILALEKRRLELSRARERYSRKLHMLLDDPMDTTLGHAAIDDGNNVRTAFVRGGQGDAISGKFQQKKAEIKAQASSQGMQKRANFCHSDSQVLPTLSGLTIARKRRVLAQFDDLQECYLQKRRRWATQLRKQCDGGLRKERDGNSISREGYHAGLEEFQSILTTFTRYSRLRVISELRHGDLFHSANIVSSIEFDRDDELFATAGVSRRIKVFDFATVVNEPADVHCPVVEMSTRSKLSCLSWNKCIKSQIASSDYEGIVTVWDVNTRQSVMMYEEHEKRAWSVDFSRTEPTRLISGSDDGKVKVWCTRQETSVLNIDMKANICCVKYNPGSSYYVAVGSADHHIHYYDLRNPSVPLYEFNGHRKTVSYVKFISTNELASAS TDSTLRLWDVRDNCLVRTFKGHTNEKNFVGLTVNSEYIA CGSETNGVFVYHKAISKPAAWHQFGSPDLDDSDDDTSHFISAVCWKSESPTMLAANSQGTIKVLVLAP 218 The amino acid sequence of SEQ IDMANYVDSKKNFKCVPALQQFYTGGPFRLSSDGSFLVCAC 487. The conserved G-proteinbeta NDEVKVVDLATGSVKNTLEGDSELIVALALTPDNKYLFS WD-40 repeat domains areASRSTQIKFWDLSSATCKRTWKAHNGPVADMACDASGGL underlined.LATAGADRSILVWDVDGGYCTHSFRGHQGVVTTVIFHPDPHCLLLFSGSDDATVRIWDLVAKKCISVLEKHFSTVTSLAISENGWNLLSAGRDKVVNIWDLRDYHCRATIPTYEPLEAVCVLPTGSRLVSVMNQSRALPENRKKSGAAPVYFLTVGERGIVRIWYSEGALCLYEQKSSDAIISSDKDELKGGFVSAVLLPLTQGVMCVTADQRFLFYNLDESDEGKCDLKVSKRLIGYNEEIVDLKFLGDEEKFLAVATNLEQVRMYDLSSMTCVYELSGHTDIVLCLDTVVFSGHSLLASGSKDHTVRIWDTESKSCICVAAGHMGAVGAVAFSKKAKNFFVSGSSDRTIKVWSFASVLDFGGISKSIKLSSQAAVAAHDKDINSVAVAPNDSLICTGSQDRTARIWRLPDLVPVLVLRGHKRGVWCVEFSPVDQCVMTASGDKTIKIWALSDGSCLKTFEGHTASVLRASFLTRGTQFVSSGADGLLKLWTIKSNECIATFDQHEDKIWAMAVGKKTEMLATGGSDSLVNLWHDCTTTDEEEALLKEEEAALKDQELLNALADTDYVKAIQLAFELRRPYKLLNVFTELYSKGHAQDQIQKVIRELGNEELRLLLEYVREWNTKPKFAHVAQFVLFQLFNVLPPKEIIEVQGISELLEGLIPYAQRHYSRIDRLMRSTFLLDYTLSSMSVLSPTETDLSSSNLLARTADPLHAQIDQFHPTHFPEPNLTPIQSLLDSGNTDSVEVTARRAKKKRVSGNDSEKTTVAEVKIGDMENAFDEPDVADQGSSRKHKPASSKKRKSIAVGNASIKRIASGNA VTIALQV 219 The amino acidsequence of SEQ ID MESSCSSMNSNRHSTEKRCLRPLQKQGASMNKHSSDRFI 488. Theconserved G-protein beta PARGSIDLDVARFMVTQKQKDNNDIHALSPSPSPSKKAY WD-40repeat domains are QKEMADTLLKNAGAADNNCRILSFNGKSSTVSQGSQENV underlined.LANLSISRRARRYIPQSADRTLDAPDLLDDYYLNLLDWSSTNVLSTALGNTVYLWDASNSSISELLIADEEEGPVTSVSWAPDGSQIAVGLNNSVVQLWDSQSNKKLRALKGHHDRVGALSWNGPILTTGGLDGIIINHDVRTRDHIVQTYKGHTQEVCGLKWSPSGQQLASGGNDNLLYIWDKSMASHNPSSQYFHQLDEHCAAVKALAWCPFQTNLLASGGGTSDGSIKFWNTQTGACLNTVDTHSQVCSLLWNRHERELLSSHGLNQNQLTLWKYPSMVKITELTGHTARVLHMAQSPDGYTVASAAADETLKFWQVFGAPDASKKTKDTKGAFNMFHMHIR 220 The amino acid sequence of SEQ IDMLDEIVADEEEEFNIWKKNTPLLYDVVITHALEWPSLTV 489. The conserved G-proteinbeta QWLPDRHQSPTKDYSLQKMIVGTHTSGDEPNYLMIAEVQ WD-40 repeat domains areMPLQYSEDGNVGGFESTEAKVHIIQQINHEGEVNRAQYM underlined.PQNSFIIATKTVSSDVYVFDYTKHSSNAPQERVCNPELILKGHTNEGYSLSWSPLKEGQLLSGSNDAQICFWDINAASGRKVVEAKQIFKVHEGAVEDVSWHLKHEYLFGSVGDDCHLLIWDTRTAAPNKPQHSVVAHESEVNSLAFNPFNEWLLATGSADKTVKLFDLRKLSCSLHTFSNHTEEVFQIEWSPMNETILASSGGDRRLMVWDLRRIGDEQTSEDAEDGPPRLIFIHGGHTSKISDFSWNLHDDWLIASVAEDNILQIWQMAEN IYHDDADIL 221 The amino acidsequence of SEQ ID MTKEDHGESRDEMGERMVNEEYKLWKKNTPFLYDLVITH 490. Theconserved G-protein beta ALEWPSLTVQWLPPSCKQQQDIIKDDDIDHPNTQMVILG WD-40repeat domains are THTSDNEPNYLILAEVQLHDGTEDEDGDGDVKRPQDKMK underlined.PGTSGGAMGKVRILQQINHQKEVNRARYMPQKPTIIATKTVNADVYVFDYSKHPSKPPQEGRCNPELRLQGHESEGYGLSWSPLKEGHLLSASDDAQICLWDITAATKAPKVVEANQIFRYHDGPVEDVAWHAIHDHLFGSVGDDHHLLLWDIRNDSEKPLHIVEAHQAEVNCLAFNPFNEWIVATGSADRTVALHDIRKLDKVLHTCAHHMEEVFQIGWSPQNGAILASCGSDRRLMVWDLSRIGDEQNPEDAEEAPPELLFIHGGHTSKISDFSWNPAEEWVIASVAEDNILQVWQMSEHIYNDDNDSPTA 222 The amino acid sequence ofSEQ ID MAMAMGDENAADPVEEFNIWKKNTPFLYDLVITHALEWP 491. The conservedG-protein beta SLTVQWLPDRHQSSTADYSLQKMIVGTHTSEDEPNYLMI WD-40 repeatdomains are AEVQIPLQNSEDNIIGGFESTEAKVQIIQKINHEGEVNK underlined.ARYMPQNSFVIATKTVSSDVYVFDYSKHPSKAPQERVCNPELILKGHSNEGYGLSWSPLKEGYLLSGSNDAQICLWDINAAFGKKVLEANQIFKVHEGAVGDVSWHLKHEYLFGSVGDDCHLLIWDMRTAAPNKPQQSVIAHQSEVNSLAFNPFNEWLLATGSMDKTVKLFDLRKLSCSLHTFSNHTDQVFQIEWSPMNETILASSGADRRLMVWDLARIGETPEDEEDGPPELLFVHGGHTSKISDFSWNLNDDRVIASVAEDNILQIWQMA ENIYHDDEDML 223 The amino acidsequence of SEQ ID MGLFEPFRALGYITDGVPFAVQRRGIETFVTLSVGKAWQ 492. Theconserved G-protein beta IYNCAKLIPVLVGPQMDKKIRALACWRDFTFAATGHDIA WD-40repeat domains are VFRRAHQVATWSGHKAKVTLLLSFGQHVLSVDLEGCLFI underlinedand the Trp-Asp (WD) WAVAEVNQNKPPIGQIQLGEKFSPSCIMHPDTYLNKVLI repeatssignature is in bold. GSEEGTLQLWNVNTRKKLYEFKGWGSSIRCCVSSPALDVVGIGCSDGKIHVHNLRYDEEIVTFMHSTRGAVTALSFRTDGQPLLAAGGSSGVISIWNLEKKKLQSVIKDAHDSSVCSLHFFANEPVLMSSATDNSIKMWIFDTTDGEARLLKYRSGHSAPPMCIRYYGKGRHILSAGQDRAFRIFSVIQDQQSRELSQGHVGKRAKKLKVKDEEIKLPPVIAFDAAEIRERDWCNVVTCHLDDPCAYTWRLQNFVIGEHILKPCLEDPTPVKSCSISACGNFAVLGTEGGWLERFNLQSGISRGTYIDIGEKRQCAHNGAVVGLACDATNTLLISGGYNGDIKVWDFKGRELKFRWEIEVPLIKIVYHPGNGILATAADDMILRLFDVTAMRLVRIFVGHMDRVTDLCFSGDGKWLLSSSMDGTIRVWDIISSRQLNAMHMDSAVTALSLSPGMDMLATTHVGHNGIYLWANRMIYSKATDIEPFISGKQVVKVSMPTVSSKRESEEGDEKRTIVAESNVNKSDVSGSLIGDSYSAQLTPELVTLALLPKAQWQSLVNLDIIKMRNKPIEPPKKPEKAPFFLPSLPTLSGERIFIPSSMNGDGDQDETRNDKTVFEARGKKLGGESLSFMQLLQSCAKIKDFTTFTNYLKGLSPSAVDMELRLLQIVDNENISETEHSVELQGIGMLLDYFVNEVSCNNNFEFVQALIRLFLKIHGETIRCQVSLQEKARKLLEIQSSTWE RLDTSFQNARCMITFLSSSQF 224 Theamino acid sequence of SEQ ID MIAAVCWVPKGVAKVLPDSAEPPTQEEIQELLKCNVVAE493. The conserved G-protein betaSDDNEDSDEESEEMDTETDKNTDAVAKALAAANALGSQS WD-40 repeat domains areSDFQRQHKVDDIANGLKELDMDHYDDEDEGIDIFGSGSL underlined and the Trp-Asp (WD)GNCYYPANDMDPYLVEQDDDDEDEIEDMTIKPSDLIILS repeats signature is in bold.ARNEDDVSHLEVWIYEEETEEGGSNMYVHHDIILPAFPLSLAWLDCNLKGGEKGNFVAVGTMQPEIELWDLDVLDEVEPAVVLGGAVKDEASGKTTKLKKKKKNKQAVNFKEGSHTD AVLGLAWNMEYRNVLASASADKSVKIWDIVAEKCEHTMQ PHTDKVQAVAWNPNQATVLLSGSFDRSVIMMDMRAPTHSGIRWPVPADVESLAWDPHTDHSFMVSAEDGTVRGFDIRAAASTADFDGKPMFILHAHDKAVCAISYNPAAPSLLTTGSTDKMVKLWDITNNQPSCIASTNPNVGAVFSAAFSKNSPFLLATGGSKGILHVWDTLDNSEVARRFGKFRPQN 225 The amino acid sequence of SEQ IDMIMDENEFCDIFSLRKRLCLLSSQEGEEEEELEAMSQLD 494. The conserved eukaryoticAGEFTVTGNEEVVAIAEDDVNTGILSQDLFSSQDYCTPS protein kinase domain isQPQDSTDLDSKDKAPCPLSPVKSTIQRKRCRPELLSNPP underlined.DSIQFSFQRLERVRSEESIQSSSQQLARVRSEVSSSDDFKTPKITASGQKNYVSQSALALRARVMSPPCIKNPYLDENEELNEKIQRSTRRSPACVTPIQSGACLSRYRADFHELEEIGRGNFSRVYKALNRLDGCCYAVKCSQSELRLDTERKVALMEVQSLAALGPHKNIVGYHTAWFENDHLYIQMELCDHNLTTANDRGILRTDTDFLEAVYQIAQALEFIHGRGVAHLDVKPENIYVRDGTYKLGDFGRATLINGTLHVEEGDARYMSREILNDNYEHLDKVDMFSLGATFFELLMRKQYPGSGKRIDRDTEIKIPILPGFSIYFQKLLQDLVSNDPGKRPSAKDV LKNPIFNKVRGAKEV 226 The aminoacid sequence of SEQ ID MLAPALEMEPVEPQSLKKLSFKSLKRALDLFSPVHGQIA 495. Theconserved G-protein beta PPDPESKKMRISYKLNFEYGGGSGSEDQVPKRKESGAAQ WD-40repeat domains are NQGQQAAGASNALALPGPEGSKIPPMEKSQNALTVGPSL underlinedand the Trp-Asp (WD) RPQGLNDVGLHGKGTAIISASGSSDRNLSTSAIMERLPS repeatssignature is in bold. RWPRPVWHPPWKNYRVISGHLGWVRSIAFDPSNQWFCTGSADRTIKIWDLASGRLKLTLTGHIEQIRGLAVSSKHTYMFSAGDDKQVKCWDLEQNKVIRSYHGHLSGVYCLALHPTIDILLTGGRDSVCRVWDIRSKMQIFALSGHDNTVCSVFAR PTDPQVVTGSHDTTIKFWDLRHGKTMTTLTNHKKSVRAM AQHPKENCFASASADNIKKFQLPRGEFLHNMLSQQKTIINTMAVNEEGVMATGGDNGSLWFWDWKSGHNFQQAHTIVQPGSLESEAGIYALSYDLTGSRLVSCEADKTIKMWKEDEL ATPETHPLNFKPPKDIRRF 227 Theamino acid sequence of SEQ ID MEEAAKEQSAGSGKPKLLRYGLRSAAKPKEDKKEEQLHQ496. The conserved G-protein betaPPPPPPPQQQAAPAPAPAATRSSTSGSAGGRDRRPQQQH WD-40 repeat domains areAVDEKYARWKSLVPVLYDWLANHNLLWPSLSCRWGPQLE underlined.QATYKNRQRLYISEQTDGSVPNTLVIANCEVVKPRVAAAEHVSQFNEEARSPFIRKYKTIIHPGEVNRIRELPQNPNIVATHTDSPDVLIWDVESQPNRHAVYGATASRPNLILTGHQENAEFALAMCPAEPFVLSGGKDKTVVLWSIQDHITASATDQTTNKSPGSGGSIIKKTGEGNEETGNGPSVGPRGIYCGHEDTVEDVAFCPSTAQEFCSVGDDSCLILWDARIGTNPVAKVEKAHNGDLHCVDWNPHDNNLILTGSADNSVNMFDRRNLTSNGVGSPVYKFEGHKAAVLCVQWSPDKPSVFGSSAEDGLLNIWDYERVDKKVDRAPNAPAGLFFQHAGHRDKIVDFHWNTADPWTMVSVSDDCDTAGGGGTLQIWRMSDLIYR PEEEVLAELENFKAHVLECSKA 228 Theamino acid sequence of SEQ ID MAKDEEEFRGEMEERLVNEEYKIWKKNTPFLYDLVITHA497. The conserved G-protein betaLEWPSLTVQWLPDREEPPGKDYSVQKMILGTHTSDNEPN WD-40 repeat domains areYLMLAQVQLPLEDAENDARQYDDERGEIGGFGCANGKVQ underlined.VIQQINHDGEVNRARYMPQNPFIIATKTVSAEVYVFDYSKHPSKPPQDGGCHPDLRLRGHNTEGYGLSWSPFKHGHLLSGSDDAQICLWDINVPAKNKVLEAQQIFKVHEGVVEDVAWHLRHEYLFGSVGDDRHLLIWDLRTSATNKPLHSVVAHQGEVNCLAFNPFNEWVLATGSADRTVKLFDLRKISSALHTFSCHKEEVFQIGWSPKNETILASCSADRRLMVWDLSRIDEFQTPEDALDGPPELLFIHGGHTSKISDFSWNPCEDWVI ASVAEDNILQIWQMAENIYHDEEDDMPPEEVV229 The amino acid sequence of SEQ IDMGKYMRKGKGVGEVAVMEVSQGSLGVRTRARTLAAASSQ 498. The conserved cyclin-KDHRRLGASKSVTTKHQSSAPPASPCVESSMHTCYLELR dependent kinase inhibitordomain SRKLEKFSRCYHSAHGATSHGESKRSLSLSEPSRLAVSE is underined.EARVASDKSSHRVLQQQSSVAHSRNNSATFSHNAKPAKAAQRKERRDDDHTSARPSEAPHEDEDGMEVEASFGENVMDLDSRERRTRETTPSSYTRDVETMETPGSTTRPPSNAGRRRFQTEGGHGTRNQFHVPTTNEIEEFFAGAEQQEQRRFTD RYNYDPVSDSPLPGRFEWVRLRP 230 Theamino acid sequence of SEQ ID MQNMEENVQSSWSLHGNKEICARYEILKRVSSGTYLDVY499. The conserved RGRRKEDGLIVALKEVHDYQSSWREIEALQRLCGCPNVVserine/threonine protein kinase RLYEVILEFLTSDLYSVIKSAKNKGENGIPEAEVKAWMIdomain is underlined, and the QILQGLANCHANWVIHRDLKPSNMLISAYGILKLADFGSserine/threonine protein kinase MSFLKRAIYEVEYELPQEDILADAPGERLMDEDDSVKGVactive-site signature is in bold.WNEGEEDSSTAVETNFDDMAETANLDLSWKNEGDMVMQGFTSGVGTRWYRAPDFLYGATIYGKEIDLWSLGCILGELLILEPLFSGTSNIDQLSRLVKVLGLQQKKNWPGCSNLPDYRKLCFPGDGSPVGLKNHVPNCSDNMFSILERLVCYDPAARLNAKEIVENKYFVEDPYPVLTHELRVPSPLREENNFSEDWAKWKDMEVDSDLENIDEFNVVHSSDGFCIKFS 231 The amino acid sequence of SEQ IDMADVPESLQQEKDEQGTDKNCCDGKFQKEIDIDDMEEEY 502. The conserved histoneNESSIDDEEENLSDNVATNNMGTTPQGQACMAVTVEGIE deacetylase family domain isHANSVGCGRNGREGSEEVTAAEDMGHVSIENIREQGRNR underlinedKSSEQLLALYEQEGLLEDDEDDDDVDWEPFEGVTVQMKWYCTNCTMANSDDSVHCDSCGEHRNSDILRQGFLASPYLPAESPSSSDVPDERLEESKCVMTTLTPSISPMIGVCCSSLQSERRTVVGFDERMLLHSEIQMETYPHPERPDRLRAIAASLRAAGLFPGKCFSIPAREATCEELQTIHSLEHVNAVESTSCGMLSHLSPDTYANEHSSLAARLAAGLCADLAKAIMTGQAQNGFALVRPPGHHAGVKDSMGFCLHNNAAIAVSASRVVGAKKVLIVDWDVHHGNGTQEIFEADQSVLYISLHRHGEGFYPGSGAVTEVGSSKGEGYSVNIPWKCGGVGDNDYIFAFQHAVLPIAEQFEPDLTIISAGFDAAKGDPLGRCEVTPDGFAHMAQMLSCLSKGKMLVILEGGYNLRSISASATAVIKVLLGDNPKALPIDIQPSKGGLQTLLEVFEIQSKYWSSLKGHDQKLRSQWEAQYGSKKRKVIRKRHMHIVGGPVWWKW GRKRVVYYHWFARVSSRKHL 232 Theamino acid sequence of SEQ ID MASGAGAAGVVEWHQKPPNPKNPVVFFDVTIGTIPAGRI503. The conserved cyclophilin- KMELFADIVPRTAENFRQFCTGEYRKAGIPIGYKGCHFHtype peptidyl-prolyl cis-trans RVIKDFMIQAGDFVKGDGSGCISIYGSKFEDENFIAKHTisomerase family domain is GPGLLSMANSGPNTNGCQFFLTCAKCDWLDNKHVVFGRVunderlined and the cyclophilin- LGEGLLVLRKIENVQTGQHNRPKLPCVIAECGEM typepeptidyl-prolyl cis-trans isomerase signature is in bold. 233 The aminoacid sequence of SEQ ID MDHYYQDDFDYLVDDEMVDFADDVEDDVRTRRRSDIDSD 505. Theconserved G-protein beta SENDFDSNNKSPDTTALQAKRGKDIQGIPWNRLNFTREK WD-40repeat domain is underlined. YRETRLQQYKNYENLPRPRRSRNLDKECTNFERGSSFYDFRHNTRSVKATIVHFQLRNLVWATSKHNVYLMQNYSIMHWSSLKQKGEEVLNVAGPIIPSVKHPGSSPQGLTRVQVSAMSVKDNLVVAGGFQGELICKYLDKPGVSFCTKISHDENGITNAVEIYNDASGATRLMTANNDLAVRVFDTEKFTVLERFSFPWSVNHTSVSPDGKLVAVLGDNADCLLADCKTGKTVGTLRGHLDYSFAAAWHPDGYILATGNQDTTCRLWDVRKLSSSLAVLKGRMGAIRSIRFSSDGRFMAMAEPADFVHLYDTRQNYTKSQEIDLFGEIAGISFSPDTEAFFVGVADRTYG SLLEFNRRRMNYYLDSIL 234 The aminoacid sequence of SEQ ID MDCSGDEEEEQFFESLEEMLSPSDSGSEAADNETGCRNA 506. Theconserved G-protein beta DARSKYEIWKRAPSSIQERRQRFLVRMGLANPSELGNQV WD-40repeat domains are NSTSAESTCSTETANIPNGIERLRENSGAVLRTAGSSGR underlined.KTHCKNVINIGLREGSVRSSSSSNGTPDVGEDNGEFGGTIFSRSGGTWECMCKIKNLDSGKEFVVDELGQDGLWNKLREVGTDRQLTMDEFERSLGLSPLVQELMRRESGVAQADCNGVHHHDAEISSSKRRSWLKALKSAAYSMRRPKEDQSNYDSERSGRRSGSFDVPWGKPQWTKVRHYRKRYKEFTALYMGQEIEAHEGSIWTMKFSLDGRYLASAGQDCVIHVREVIESMRTFGADTPDLYASSAYFSMNGLQELVPLSIEDHANKMKRGKIIGSKKSSNSDCIVLPNKVFQLSEEPVCSFHGHLLDVFDLSWSPSQYLLSSSMDKTVRLWKLGHESCLKVFSHNDIVTCIQFNPVDERYFISGSLDGKARIWSIPDRQVVDWSDLREMVTAVCYTPDGQGGLVGSIKGSCRFYNTSGNKLQLENQLNVRSKKKKSSGKKITGFQFAPGGDSQKVLITSADSRVRVYNGSELVCKYKGFRNTCSQISASFAPNGQHFVCASEDSRVYIWNHESPRGSGARHEKSSWSHEHFLSQGVSVAIPWSGMKLQPPVWNSPEFMLGQRHNLLSLQGGKDVGCQNGLLSREAGEGQESETPLHYISQVSHSCGSQNMVDRDGQDDLSRYSACISDSRLSSFMAFPESPGNPDDLNSKVFFSDSSSKGSATWPEEKLPPTRKQSRSNSTSSHYDTLKTHLGNTIQGQSGASAAVAWGLVIVTAGHGGEIRSFQNYGLPVRL 235 The amino acid sequence of SEQID MPSIPAIGEFTVCEINRELLTTKDESDTQAKDAYAKILG 507. The conserved G-proteinbeta LVFPPISFQIEEGFGSASRQQFDQDLDREDTIVTPSTSE WD-40 repeat domain isunderlined. GTNALQEGGLLLKGVSVLKNILASSFGPIFSPNDTKVLKKVELLQGISWHRHKHILAFISGSNQVTVHDFQDPEWRESSLLVSESQRGIEALEWRPNGGTTLSVACRGGICIWSASYPGSVAPVRSGVASFLGTSTRGSSVRWTLVDFLQIPGGKAVTALSWSPTGRLLASASREDSSFTIWDVAQGVGTPLRRGLGGISLLKWSPTGDYLFSAKPNGTFYLWETNTWTLEQWSSSGGCVISATWGPDGRMLFMAFSESTTLGSLHFAGRPPSLDAHLLPMELPEIGSITGGFGNIEKMAWDGCGERLAVSYTGGDLMYVGLIAIYDTRRTPFISASLVGFIRGPGEQVKPLAFAFHDKFKQGPLLSVCWSSGLCCTYPLIFRAH 236 The amino acid sequence of SEQ IDMEEENAKHTEETRQVQVRFTTKLQPALRVPTTSIAIPAH 508. The conserved G-proteinbeta LTRYGLSDIVNTLLGNDKPQPFDFLVESELVRTSLEKLL WD-40 repeat domains areLIKGISAEKILNIEYILAVVPPKQEEPSLHDDWVSVVDG underlined.SYPNFIFSGSFDSIGRIWKGEGLCTHVLEGHRDAITSAAFIMPSDSSDSFINLATASKDRTLRLWQFKPNEHMTNGKMVRPYKLLKGHTSSVQTVSACPRRNLICSGSWDCSIKIWQTAGEMDIESNAGSVKKRKLEDSTEQIISQIEASRTLEGHSQCVSSVVWLEKDTIYSASWDHSVRSWDVETGVNSLTVGCRKALHCLSIGGEGSALIAAGGADSVLRIWDPRMPGTFTPILQLSSHKSWITACKWHPKSRHHLISASHDGTLKLWDVRSKVPLTTLEAHKDKVLCADWWKEDCVISGGADSTLQIF SNLNLT 237 The amino acidsequence of SEQ ID MNRLRSKRNHILELRLGQSEPEKEATLASNRSRGTNAPI 509. Theconserved RING-type zinc VVEDDDDVVVSSPRSFALARSSVSQRSSRIPIVNEEDLE fingeris underlined. LRLGLAVTGRTSAEHNPRRRHGRVPPNKPIVLCDDAGEADQSSSKKRRTGQQLSSDVQSDESKEVKLTCAICISTMEEETSTICGHIFCKKCITNAIHRWKRCPTCRKKLAINNIIHR IYISSSTG 238 The amino acidsequence of SEQ TD MEEPPPPAVLPSSEDTSIVSSHSFVNAPPTVPVGLDASI 510. Theconserved G-protein beta PQISTPGINQPGLTIPVPPEAAPLTASLVAASAGMPPAV WD-40repeat domains are VPSFVRPAIVAHPSVMPPPSMPLAALPMPVASAVPVAAP underlinedand the splicing factor HFPPSTPNDNSITPSMPVPTPIVASSSVPPSVTIPGIAP motif isin bold. LPFIAPIPVPSSRPVAPSPFMPPARPLGASVSVAMDVDNTDEQDQDADNKGESPSSSPDHPEDPSAAEYEITEESRKVRERQEQAIQELLLRRRAYALAVPTNDSSVRARLRRLNEPITLFGEREMERRDRLRALMAKLDAEGQLEKLMKVQEEEEAAANVDAEEVQEMEGPQVYPFYTEGSQELLKARTEITKFSLPRAVSRLQRARRKREDPDEDEDEELKCVLQQSAQINMDCSEIGDDRPLSGCAFSSDGTLLATSAWSGVTKLWSVPNINKVATLKGHTERVTDVAFSPTNCHLATACADRTAMLWNSEGVLMKTYEGHLDRLARLAFHPSGLYLGTASFDKTWRLWDVNTGIELLLQEGHSRSVYGIAFQCDGSLAATCGLDGLARIWDLRTGRSILALEGHVKPVLGIDFSPNGYHLATGSEDHTCRIWDLRKRQSVYIIPAHSHLVSQVKFEPQEGYFLVTASYDSTAKVWSARDFKSIKVLAGHEAKVTSVDITADGQ YIATVSHDRTIKLWSSKNSTNDMNIG 239The amino acid sequence of SEQ IDMKRAYKLQEFVAHASNVNCLKIGKKSSRVLVTGGEDHKV 511. The conserved G-proteinbeta NMWAIGKPNAILSLSGHSSAVESVTFDSAEALVVAGAAS WD-40 repeat domains areGTIKLWDLEEAKIVRTLTGHRSNCISVDFHPFGEFFASG underlined and the Trp-Asp (WD)SLDTNLKIWDIRRKGCIHTYKGHTRGVNSIRFSPDGRWV repeats signature is in bold.VSGGEDNIVKLWDLTAGKLMHDFKCHEGQIQCMDFHPQE FLLATGSADRTVKFWDLETFELIGSAGPETTGVRAMIFN PDGRTLLTGLHESLKVFSWEPLRCYDAVDVGWSKLADLNIHEGKLLGCSYNQSCVGVWVVDISRVGPYAAGNVSRTNGHNEAKLASSGHPSVQQLDNNLKTNMARLSLSHSTESGIKEPKTTTSLTTTEGLSSTPQRAGIAFSSKNLPASSGPPSYVSTPKKNSTSRVQPTTNFQTLSRPDIVPVIVPRSNSLRPETTSDAKKEMNNFGRVVPSTVSTKSTDVIKSGSNRDESDKIDSINQKRMTGNDKTDLNIARAEQHVSSRLDNTNTSSVVCDGNQPAARWIGAAKFRRNSPVDPVVSPHDRSPTFPWSATDDGVTCQPDRQVTAPELSKRVVEPGRARALVASWETREKALTADTPVLVSGRPPTSPGVDMNSFIPRGSHGTSESDLTVSDDNSAIEELMQQHNAFTSILQARLTKLQVIRRFWQRNDLKGAIDATGKMGDHSVSADVISVLIERSEIFTLDICTVILPLLTRLLQSETDRHLTVAMETLLVLVKTFGDVIRATISATPTIGVDLQAEQRLERCNLCYVELENIKQILVPLI RRGGAVAKSAQELSLALQEV 240 Theamino acid sequence of SEQ ID MAGSDENNPGVVGGAHVQEGLRVGAGKMGAGNVQQRRAL512. The conserved cyclin N- and SNINSNIIGAPPYPCAVNKRVLSEKNVNSENDLLNAAHRC-terminal family domains are PITRQFAAQMAYKQQLRPEENKRTTQSVSNPSKSEDCAIunderlined. LDVDDDKMADDFPVPMFVQHTEAMLEEIDRMEEVEMEDVAEEPVTDIDSGDKENQLAVVEYIDDLYMFYQKAEASSCVPPNYMDRQQDINERMRGILIDWLIEVHYKFELMDETLYLTVNLIDRFLAVQPVVKKKLQLVGVTAMLLACKYEEVSVPVVEDLILISDRAYSRKEVLEMERLMVNTLHFNMSVPTPYVFMRRFLKAAQSDKKLELLSFFIIELSLVEYDMLKFPPSLLAASAIYTALSTITRTKQWSTTCEWHTSYSEEQLLECARLMVTFHQRAGSGKLTGVHRKYSTSKFGHAARTEPANFL LDFRL 241 The amino acidsequence of SEQ ID MQAPREGKSAAAIVGMGKYMKKSKAIPRDVSLLEASPRS 513. Theconserved cyclin- PSATGVRTRAKTLASRRLRRASQRRPPPPAAAAAAAAPS dependentkinase inhibitor domain LDASPCPFSYLQLRSRRLRRPRLAPSPEARIDEGPAGSG isunderlined. SRGSRDASCSARTASSSGGVEGEGACVGRGDRGNGGECVRDAAVDASYGENDLEIEDRDRSTRESTPCSLIRDSNANTPPGSTTRQQSSCTAHRTQMSILRSIPTSDEMEEFFAYAE QRQQRSFIEKYNFDIVKDRPLPGRFEWVQVIP242 The amino acid sequence of SEQ IDMDGHSSHLAAQNRSRGSQTPSPSHSAASASATSSIHLKR 514. The conserved GCN5-relatedN- KLSAANASAASAAAAAAAAAAAADDHAPPFPPSSISADT acetyltransferase familydomain is RDGALTSNDDLESISARGGGAGDDSDDDSDDEEEDDGDN underlined and thebromodomain is DGGSSLRTFTAARLENVGPAAARNRKIKAESNATVKVEK in bold.EDSAKDGGNGAGVGALGPAATSGAGSGSGTVPKEDAVKIFTENLQASGAYSAREENLKREEEAGRLKFECLSNDGVDDHMVWLIGLKNIFARQLPNMPKEYIVRLVMDRNHKSVMVIRRNLVVGGITYRPYASQKFGEIAFCAIKADEQVKGYGTRLMNHLKQHARDVDGLTHFLTYADNNAVGYFIKQGFTKEIYLDKDRWHGYIKDYDGGILMECKIDPKLPYTDLSTMVRRQRQAIDEKIRELSNCHIVYQGIDFQKRDAGVPQNTIKMEDIPGLREAGWTPDQWGYSRFRGLSDQKRLTFFIRQLLKVLNDHSDAWPFKEPVDAREVPDYYDIIKDPMDLKTMTKRVESEQYYVTLEMFIADVKRMFANARTYNSPDTIYFKIATR LEAHFQSKVQSNLQSGAGKIQQ 243 Theamino acid sequence of SEQ ID MFNGMMDPELFKLAQEQMNRMSPAELAKIQQQMMSNPEL515. The conserved TPR repeat MRMASESMKNMRPEDLRQAAEQLKHVRPEEMAEIGEKMAdomain is underlined NASPEEIAAVRARADAQMTYEINAAKILKKEGNELHSQGRFKDASQKYLRAKNNLKGIPSSEGKNLLLACSLNLMSCYLKTRQYEECIKEGSEALACEEKNLKAFYRRGQAYRELGQLKDAVSDLRKAHEISPDDETIAQVLRDTEESLTKEGGSAPRGVVIEEITEEDETLASVNHESPSEYSEKRHQESEDAHKGPINGDIMGQMTNSESLKALKGDPDAIRSFQNFISNADPTTLAAMGAGNAGEVSPDLIKTASSMIGKMSAEELQKMIQLASSFPGENPYVTRNSDSNSNSFGNGSIPNVSPDMLKTASDMMSKMSPDDLQRMFEMASSSRGKDPSLDANHASSSSGANLAANLNHILGESEPSSSYHIPSSSRNISSSPLSNFPSSPGDMQEQIRNQMKDPAMRQMFTSMMKNMSPEMMANMGKQFGLELSPEDAAKAQEAMSSLSPEMLDKMMRWADRAQRGVETAKKTKNWLLGRPGMILAICMLLLAVILHRLGFIGS 244 The amino acid sequence ofSEQ ID MIAAISWVPRGASKAVPEVAEPPSKEEIEEILKSGVVER 516. The conservedG-protein beta SGDSDGEEDDENMDAVASEKADEVSTALSAADALGRISK WD-40 repeatdomains are VTKAGSGFEDIADGLRELDMDNYDEEDEDVKLFSTGLGD underlined.LYYPSNDMDPYLKDKDDDDDTEEIEDLSIKPMDSLIVCARTDDEVNLLEVYLLEPSLSDESNMYVHHEVVISEFPLCTAWLDCPIKGGDKGNFIAVGSMEPAIEIWDLDIIDAVEPCLVLGGQEELKKKKKKGKKASIKYKEGSHTDSVLGLAWNKEFRNILASASADRQVKIWDVAAGKCNITMEHHTDKVQAVAWNHHAPQVLLSGSFDHSVVMKDGRIPSHSGYRWSVTADVESLAWDPHSEHFFVVSLEDGTVRGFDVRAAISNSASQSLPSFTLHAHEKAVSTISYNPAAPNLLATGSTDKMVKLWDLSNNQPSCIASRNPKAGAVFSVSFSEDSPLLLAIGGSKG RLEVWDTSSDAAVSRRFGKHGKPKTAEPGS245 The amino acid sequence of SEQ IDMKFCKKYQEYMQGQEGKKLPGLGFKKLKKILKRCRRRDS 517. The conserved Zn-finger,RING LHSQKALQAVQNPRTCPAHCSVCDGSFFPSLLEEMSAVL domain is underlined, andthe SPX, GCFNKQAQKLLELHLASGFQKYLMWFKGKLRGNHVALIQ N-terminal is in boldEGKDLVTYALINAIAIRKILKKYDKIHLSTQGQAFKSQVQRMHMEILQSPWLCELIAFHINVRETKANSGKGHALFEGCSLVVDDGKPSLSCELFDSIKLDIDLTCSICLDTVFDSVSLTCGHIYCYMCACSAASVTIVDGLKAAEPKEKCPLCREARVFEGAVHLDELNILLSRSCPEYWAERLQTERVERVRQ AKEHWESQCRAFMGVE 246 The aminoacid sequence of SEQ ID MVSTQSTRENPSIFFPPPLKPWLLPVVLSLSLSRQLGMA 518. Theconserved G-protein beta AAAAASLPFKKNYRSSQALQQFYAGGPFAVSSDGSFIAC WD-40repeat domains are NCGDSIKIVDSSNASLRPSIDCGSDTITALSLSPDGKLL underlined.FSAGHSRQIRVWDLSTSTCLRSWKGHDGPVMSMACPVSGGLLATGGADRKVMVWDVDGGFCTHFFKGHDGVVSTVLFHPDSNRSLLFSGSDDGTIRVWDLLAKKCASTLRGHDSTVTSLAFSEDGLTLLAAGRDKVVSLWDLHNYACKKTIPMYEVLESVCVIHSGTVLASQLGLDDQLKVTKESAQNIHFITVGERGILRIWKSEGSVCLFKQEHSDVTVISDEDDSRSGFTAAVMLPLDQGLLCVTADQQFLFYYPEKHPEGIFSLTLCRRLVGYNEEIVDMKFLGEEENFLAVATNLEQVRVYELASMSCSYVLAGHTETVLCLDTCISSSGRTLIVTGSKDNSVRLWDSESRHCIGVGVGHMGAVGAVAFSRKRQDFFVSGSSDRTLKVWSLDGISEDGVDSTNLKAKAVVAAHDKDINSVAVAPNDSLVCSGSQDRTACVWRLPDLVSVVVLKGHKRGIWSVEFSPVDQCVLTASGDKTVKIWAISDGSCLKTFEGHVSSVLRASFLTRGTQFVSCGADGLVKLWTVRTNECIATYDQHSDKVWALAVGKKTEMLATGGSDAVVNLWYDSTASDKEDAFRKEEEGVLKGQELENAVSDADYTKAIELALELRRPHKLFELFSELCRTREVGDRVERILSALSGEEVCLLLEYIREWNAKPKLCHVAQSVLSQVFRILSPTEIVEIKGIGELLEGLIPYSQRHFSRIDRLVRSTYLLDYTLTGMSVIEPEADRSAVNDGSPDKSGLEKLEDGLLGENVGEEKIQNKEELESSAYKK RKLPRSKDRSKKKSKNVVYADAAAISFRA247 The amino acid sequence of SEQ IDMDSAPRRKSGGINLPSGMSETSLRLDGFSGSSSSFRAIS 519. The conserved G-proteinbeta NLTSPSKSSSISDRFIPCRSSSRLHTFGLVERGSPVKEG WD-40 repeat domains areGNEAYSRLLKAELFGSDFGSLSPAGQGSPMSPSKNMLRF underlined.KTESSGPNSPFSPSILRQDSGFSSEASTPPKPPRKVPKTPHKVLDAPSLQDDFYLNLVDWSSQNTLAVGLGTCVYLWSASNSKVTKLCDLGPNDGVCAVQWTREGSYISIGTSLGQVQIWDGTQCKRVRTMGGHQTRTGVLAWNSRILASGSRDRVILQHDLRVPNEFIGKLVGHKSEVCGLKWSHDDRELASGGNDNQLLVWNQHSQQPVLKLTEHTAAVKAIAWSPHQNGLLASGGGTADRCIRFWNTTNGHQTSSVDTGSQVCNLAWSKNVNELVSTHGYSQNQIMVWKYPSMAKVATLTGHSLRVLYLAMSPDGQTIVTGAGDETLRFWNVFPSAKAPAPVKDTGLW SLGRTHIR 248 The amino acidsequence of SEQ ID MEDEAEIYDGVRAQFPLTFGKQSKPQTSLESVHSATRRG 520. Theconserved G-protein beta GPAPAPAPASSSSLPSTTSPSAAGGAGKSSGLPSLSSSS WD-40repeat domains are TAWLEGLRAGNPRAGREAGIGSRGGDGEDGGRAMIGPPR underlined.PPPGFSANDDGGGEDDDDDGDGVMVGPPPPPPGNLGDGDDDEEEEEAMIGPPRPPVVDSDEEEEEEEEENRYRLPLSNEIVLKGHNKIVSALAVDPTGSRVLSGSYDYTVRMFDFQGMNSRLSSFRDFEPVEGHQVRNLSWSPTADRFLCVTGSAQAKIYDRDGLTLGEFVKGDMYIRDLKNTKGHITGLTWGEWHPKTKETILTSSEDGSLRIWDVNDFKSQKQVIKPKLARPGRVPVTTCTWDREGKCIAGGIGDGSIQIWNLKPGWGSRPDIHVEQAHADDITGLKFSSDGKILLTRSFDDSLKVWDLRLMKNPLKVFEDLPNHYAQTNIACSPDEQLFLTGTSVERESTIGGLLCFFDRSKLELVSRIGISPTCSVVQCAWHPRLNQIFATSGDKSQGGTHVLYDPTLSERGALVCVARAPRKKSVDDFELKPVIHNPHALPLFRDQPSRKRQREKILKDPLKSHKPELPMNGPGHGGRVGASKGSLLTQYLLKQGGMIKETWMDEDPREAILKHADAAEKNPKFTRAYAETQPDPVFAKSD SEDEDK

TABLE 12 Eucalyptus in silico Data. SEQ ConsID ID eucSpp Family 1 2 3 45 6 7 8 9 10 11 12 1 3910 Cyclin- 0.25 0.11 0.20 0.73 dependant proteinkinase 2 19213 Cyclin- 0.59 0.64 dependant protein kinase 3 36800Cyclin- 0.11 0.36 dependant protein kinase 4 40260 Cyclin- 0.85dependant protein kinase 5 41965 Cyclin- 0.35 0.86 dependant proteinkinase 6 2906 Cyclin- 0.93 0.81 dependant protein kinase 7 1518 Cyclin-0.08 0.28 0.08 0.06 0.11 dependant protein kinase 8 8078 Cyclin- 0.173.20 dependant protein kinase 9 9826 Cyclin- 0.36 0.23 0.15 0.04 0.240.43 dependant protein kinase 10 10364 Cyclin- 0.11 1.52 0.13 dependantprotein kinase 11 11523 Cyclin- 0.15 0.06 0.15 2.40 dependant proteinkinase 12 24358 Cyclin- 0.76 0.07 0.04 0.24 dependant protein kinase 1339125 Cyclin- 0.23 dependant protein kinase 14 5362 Cyclin- 0.68 0.060.08 1.17 dependant protein kinase 15 44857 Cyclin- 0.68 0.06 0.08 1.17dependant protein kinase 16 1743 Cyclin A 0.19 2.10 0.06 0.15 17 12405Cyclin A 0.06 0.59 2.84 18 3739 Cyclin B 0.42 1.99 0.08 2.33 19 22338Cyclin B 0.86 20 28605 Cyclin B 0.39 0.04 0.47 21 41006 Cyclin B 0.71 226643 Cyclin D 0.85 0.83 0.06 1.06 0.08 0.26 23 45338 Cyclin D 2.03 2446486 Cyclin D 0.30 25 12070 Cyclin- 0.24 0.82 0.06 0.26 0.92 dependentkinase regulatory subunit 26 6617 Histone 0.08 0.06 0.04 0.55 0.51 0.26acetyltransferase 27 7827 Histone 2.27 0.11 0.04 acetyltransferase 288036 Histone 1.16 acetyltransferase 30 1596 Histone 0.17 0.16 0.08 2.980.88 0.26 0.98 0.71 deacetylase 31 5870 Histone 0.19 0.17 0.12 5.43deacetylase 32 6901 Histone 1.21 0.08 2.01 1.16 0.08 deacetylase 33 6902Histone 0.08 0.11 1.21 0.47 deacetylase 34 7440 Histone 0.48 1.23 0.150.22 0.48 0.20 2.02 deacetylase 35 8994 Histone 0.09 0.15 deacetylase 3624580 Histone 0.42 1.22 deacetylase 37 37831 Histone 0.08 0.22 0.40 1.190.12 deacetylase 38 34958 MAT1 CDK- 0.15 0.23 activating kinase assemblyfactor 39 22967 Peptidyl- 0.72 0.69 prolyl cis- trans isomerase 40 8599Peptidyl- 0.46 0.08 0.50 0.17 0.51 0.28 3.01 prolyl cis- trans isomerase41 9919 Peptidyl- 0.51 0.35 0.06 0.15 0.43 4.24 prolyl cis- transisomerase 42 15820 Peptidyl- 0.04 6.78 prolyl cis- trans isomerase 438327 Peptidyl- 0.06 0.04 6.86 prolyl cis- trans isomerase 44 4604Peptidyl- 0.68 prolyl cis- trans isomerase 45 966 Peptidyl- 0.59 1.020.54 0.69 0.50 0.93 0.59 0.95 18.65 prolyl cis- trans isomerase 46 1037Peptidyl- 0.59 prolyl cis- trans isomerase 47 4603 Peptidyl- 0.17 0.171.24 0.04 0.34 prolyl cis- trans isomerase 48 5465 Peptidyl- 1.21 0.080.66 0.11 0.29 0.16 6.99 prolyl cis- trans isomerase 49 6571 Peptidyl-0.51 0.08 0.41 0.08 1.14 prolyl cis- trans isomerase 50 6786 Peptidyl-0.42 0.33 0.06 0.41 0.04 prolyl cis- trans isomerase 51 7057 Peptidyl-0.42 0.11 0.04 prolyl cis- trans isomerase 52 8670 Peptidyl- 1.56 0.390.20 0.12 prolyl cis- trans isomerase 53 9137 Peptidyl- 0.04 0.59 prolylcis- trans isomerase 54 10285 Peptidyl- 0.60 1.16 0.04 0.04 0.45 prolylcis- trans isomerase 55 10600 Peptidyl- 0.16 0.17 0.06 0.46 prolyl cis-trans isomerase 56 11551 Peptidyl- 0.08 0.06 0.04 0.08 1.89 prolyl cis-trans isomerase 57 20743 Peptidyl- 0.76 prolyl cis- trans isomerase 5823739 Peptidyl- 0.59 prolyl cis- trans isomerase 60 31985 Peptidyl- 1.99prolyl cis- trans isomerase 61 32025 Peptidyl- 0.99 prolyl cis- transisomerase 62 32173 Peptidyl- 1.99 prolyl cis- trans isomerase 64 9143Retinoblastoma 0.90 0.15 related protein 65 349 WD40 repeat 0.24 0.340.08 0.17 0.22 0.33 0.08 0.25 2.24 protein 66 575 WD40 repeat 0.25 0.940.31 0.34 0.11 0.16 0.47 1.87 protein 67 804 WD40 repeat 0.15 0.34 0.390.33 0.39 1.82 protein 68 805 WD40 repeat 0.97 0.51 4.66 0.23 0.17 0.770.33 1.07 0.24 4.43 protein 69 806 WD40 repeat 0.83 0.04 protein 70 2248WD40 repeat 0.08 0.08 1.92 0.06 0.08 0.91 protein 71 3203 WD40 repeat0.34 0.18 0.15 0.17 0.11 0.30 0.04 0.72 protein 72 3209 WD40 repeat 0.080.15 0.17 0.12 0.61 protein 73 4429 WD40 repeat 0.08 1.16 0.08 0.13protein 74 4607 WD40 repeat 0.76 0.54 0.06 0.07 protein 75 4682 WD40repeat 0.08 0.28 0.23 1.13 0.08 0.12 protein 76 5786 WD40 repeat 0.080.06 0.46 0.08 0.13 protein 77 5887 WD40 repeat 1.61 1.23 0.08 0.06 0.150.28 1.41 protein 78 5981 WD40 repeat 0.08 0.37 protein 79 6766 WD40repeat 0.24 0.08 1.31 0.51 0.06 0.74 0.51 0.28 protein 80 6769 WD40repeat 0.93 0.17 0.12 2.28 protein 81 6907 WD40 repeat 0.25 0.17 0.060.45 0.32 0.47 1.67 protein 82 7518 WD40 repeat 0.91 0.28 0.15 0.55 0.59protein 83 7717 WD40 repeat 0.47 0.38 protein 84 7718 WD40 repeat 0.241.88 0.08 0.22 0.04 0.92 protein 85 7741 WD40 repeat 1.42 0.11 0.47protein 86 7884 WD40 repeat 1.33 0.15 0.24 protein 87 8258 WD40 repeat0.72 0.19 0.23 0.87 0.15 0.08 0.08 protein 88 8465 WD40 repeat 0.47 0.081.75 protein 89 8616 WD40 repeat 0.57 0.08 0.69 0.16 0.13 protein 908690 WD40 repeat 0.26 0.08 0.35 1.39 0.34 0.32 2.13 0.80 protein 91 8708WD40 repeat 0.57 0.04 protein 92 8850 WD40 repeat 0.09 0.06 0.27 2.03protein 93 9072 WD40 repeat 1.21 0.17 0.48 protein 94 9465 WD40 repeat0.24 0.72 0.33 0.15 protein 95 9472 WD40 repeat 0.36 1.99 0.11 0.61 6.90protein 96 9550 WD40 repeat 0.90 0.11 1.78 protein 97 10284 WD40 repeat0.24 0.08 1.82 1.22 0.16 0.47 0.28 protein 98 10595 WD40 repeat 0.160.17 0.11 6.52 0.85 protein 99 10657 WD40 repeat 0.06 0.12 protein 10012636 WD40 repeat 0.06 0.65 protein 101 12748 WD40 repeat 1.50 0.08 0.061.67 0.04 0.38 protein 102 12879 WD40 repeat 0.08 0.33 0.06 0.04 0.082.00 protein 103 15515 WD40 repeat 0.35 0.30 protein 104 15724 WD40repeat 0.25 0.33 0.15 0.47 0.04 0.39 protein 105 16167 WD40 repeat 0.240.52 protein 106 16633 WD40 repeat 1.96 0.12 0.42 protein 107 17485 WD40repeat 0.65 protein 108 18007 WD40 repeat 0.12 protein 109 20775 WD40repeat 0.17 0.08 protein 110 23132 WD40 repeat 2.42 protein 111 23569WD40 repeat 0.91 0.91 protein 112 23611 WD40 repeat 4.15 protein 11324934 WD40 repeat 0.34 0.04 protein 114 25546 WD40 repeat 0.09 protein115 30134 WD40 repeat 0.07 protein 116 31787 WD40 repeat 0.19 1.19protein 117 34435 WD40 repeat 0.35 0.08 protein 118 34452 WD40 repeat1.44 0.20 0.25 protein 119 35789 WD40 repeat 0.20 protein 120 35804 WD40repeat 0.19 0.27 0.08 protein 121 43057 WD40 repeat 0.30 0.57 protein122 46741 WD40 repeat 0.46 protein 123 47161 WD40 repeat 1.78 protein235 6366 WD40 repeat 0.08 0.68 0.23 0.93 0.11 0.36 0.83 0.24 0.94protein 236 17378 WD40 repeat 0.65 0.12 0.08 protein 252 45414 Cyclin B3.13 253 44328 Cyclin- 0.38 dependant kinase inhibitor 254 15615 Histone0.22 0.04 acetyltransferase 255 17239 Peptidyl- 0.08 0.50 0.08 prolylcis- trans isomerase 256 18643 WD40 repeat 0.04 0.90 protein 257 19127WD40 repeat 0.04 0.89 protein 258 22624 WD40 repeat 1.16 protein 25932424 WD40 repeat 0.50 protein 260 37472 WD40 repeat 0.08 0.17 proteinIn Table 12, the following numbers 1-12 represent the following tissues:1 is bud reproductive; 2 is bud vegetative; 3 is cambium; 4 is fruit; 5is leaf 6 is phloem; 7 is reproductive; 8 is root; 9 is sap vegetative;10 is stem; 11 is whole; and 12 is xylem.

TABLE 13 Pine in silico data. ConsID SEQ pinus ID Radiata Family 1 2 3 45 6 7 8 9 10 11 12 124 1766 Cyclin- 1.02 0.05 1.58 0.15 0.22 0.22 0.182.16 4.91 dependant protein kinase 125 2927 Cyclin- 0.16 0.19 0.11 0.140.04 0.36 0.38 0.17 dependant protein kinase 126 7642 Cyclin- 0.22 0.210.05 0.07 dependant protein kinase 127 13714 Cyclin- 0.11 0.11 dependantprotein kinase 128 16332 Cyclin- 0.54 0.26 0.14 0.04 0.91 dependantprotein kinase 129 21677 Cyclin- 0.05 0.14 0.17 dependant protein kinase130 27562 Cyclin- 0.41 dependant protein kinase 131 1504 Cyclin- 0.160.36 0.35 0.21 0.54 0.09 0.65 dependant protein kinase 132 15211 Cyclin-0.13 0.15 0.19 0.19 dependant protein kinase 133 20421 Cyclin- 0.04 0.050.95 dependant protein kinase 134 3187 Cyclin- 0.34 0.15 0.04 0.18 0.38dependant protein kinase 135 15661 Cyclin- 0.04 0.13 dependant proteinkinase 136 13874 Cyclin A 0.31 0.27 0.15 0.05 137 14615 Cyclin A 0.160.15 138 4578 Cyclin B 0.47 0.14 0.13 0.22 0.74 0.38 139 23387 Cyclin B0.29 0.26 0.17 140 6970 Cyclin D 0.14 0.27 0.04 141 10322 Cyclin D 0.160.19 0.06 0.14 1.12 1.36 142 22721 Cyclin D 0.27 0.36 143 23407 Cyclin D0.15 0.26 0.31 144 1945 Cyclin- 0.28 0.55 0.41 0.16 1.62 5.02 0.22 0.720.39 3.06 dependent kinase regulatory subunit 145 8233 Cyclin- 0.21dependent kinase regulatory subunit 146 8234 Cyclin- 0.16 0.11 dependentkinase regulatory subunit 147 22054 Cyclin- 0.05 0.22 0.18 dependentkinase regulatory subunit 148 12137 Histone 0.06 1.51 0.19acetyltransferase 149 12582 Histone 0.64 0.15 1.09 0.33 0.63acetyltransferase 150 15285 Histone 0.21 0.12 0.70 0.14acetyltransferase 151 17229 Histone 0.94 0.16 acetyltransferase 15220724 Histone 0.04 0.19 0.19 acetyltransferase 153 4555 Histone 0.160.14 0.97 0.14 0.89 0.89 deacetylase 154 4556 Histone 0.14 deacetylase155 5729 Histone 0.31 0.28 0.22 0.58 0.22 2.00 0.48 0.07 0.04 2.73 1.46deacetylase 156 7395 Histone 0.14 0.14 0.19 0.93 0.04 0.14 1.33deacetylase 157 9503 Histone 0.11 0.14 deacetylase 158 11283 Histone0.19 0.15 0.96 1.35 deacetylase 159 12322 Histone 0.16 0.06 0.11 0.040.05 0.29 deacetylase 161 23236 Histone 0.13 0.11 deacetylase 162 171Peptidyl- 0.07 0.46 prolyl cis-trans isomerase 163 172 Peptidyl- 0.190.11 0.18 0.11 0.46 prolyl cis-trans isomerase 164 1480 Peptidyl- 2.514.20 0.88 2.97 1.58 3.53 7.36 1.33 2.74 0.72 6.62 10.14 prolyl cis-transisomerase 168 1692 Peptidyl- 0.16 0.22 0.65 0.61 0.26 0.29 0.18 1.280.34 prolyl cis-trans isomerase 169 5313 Peptidyl- 0.14 0.07 0.37 0.17prolyl cis-trans isomerase 170 6362 Peptidyl- 0.14 0.33 0.05 0.06 0.600.04 2.92 0.68 prolyl cis-trans isomerase 171 6493 Peptidyl- 0.42 0.110.21 0.11 0.04 0.25 0.32 prolyl cis-trans isomerase 172 6983 Peptidyl-0.61 0.13 0.04 prolyl cis-trans isomerase 174 7665 Peptidyl- 0.11 0.390.05 0.62 0.25 prolyl cis-trans isomerase 175 12196 Peptidyl- 0.19 0.150.14 0.16 prolyl cis-trans isomerase 176 13382 Peptidyl- 0.25 0.06 0.070.04 0.87 0.15 prolyl cis-trans isomerase 177 16461 Peptidyl- 0.19 0.150.15 0.04 0.04 0.74 prolyl cis-trans isomerase 178 17611 Peptidyl- 0.240.11 0.27 0.41 0.99 prolyl cis-trans isomerase 179 19776 Peptidyl- 0.130.07 0.16 0.05 0.61 prolyl cis-trans isomerase 180 20659 Peptidyl- 0.150.19 prolyl cis-trans isomerase 181 22559 Peptidyl- 0.11 0.14 0.20prolyl cis-trans isomerase 182 24188 Peptidyl- 0.23 prolyl cis-transisomerase 183 27973 Peptidyl- 1.01 prolyl cis-trans isomerase 184 1353WD40 0.44 0.05 0.73 0.11 1.07 0.70 1.32 repeat protein 185 1978 WD400.14 0.05 0.44 0.11 0.21 0.27 0.36 1.46 0.82 repeat protein 186 2810WD40 0.42 0.79 0.11 0.39 0.27 0.36 1.69 1.03 repeat protein 187 2811WD40 0.14 0.09 0.14 repeat protein 188 2812 WD40 0.15 0.18 0.04 0.16repeat protein 189 3514 WD40 0.63 0.06 0.14 0.18 0.48 0.56 repeatprotein 190 4104 WD40 0.14 0.25 0.27 0.37 0.36 0.19 0.18 0.39 0.53repeat protein 191 5595 WD40 0.14 0.25 0.15 0.14 0.07 0.23 repeatprotein 192 5754 WD40 0.31 0.14 0.06 0.07 0.16 0.10 0.16 repeat protein193 6463 WD40 0.16 0.56 0.22 0.43 0.81 0.53 0.21 0.08 1.00 0.70 repeatprotein 194 6665 WD40 0.31 0.28 0.45 0.44 0.96 0.07 3.37 2.68 repeatprotein 195 6750 WD40 0.14 0.59 0.05 0.37 0.42 0.04 0.18 0.52 repeatprotein 196 7030 WD40 0.31 0.40 0.54 0.45 0.37 0.07 1.58 3.41 repeatprotein 197 7854 WD40 0.11 0.14 0.05 repeat protein 198 7917 WD40 0.220.39 0.13 0.15 0.18 0.56 repeat protein 199 7989 WD40 0.11 0.04 0.11repeat protein 200 8506 WD40 0.47 0.33 0.11 0.86 0.19 1.28 0.04 1.233.12 repeat protein 201 8692 WD40 0.21 0.06 0.11 0.15 0.10 0.87 repeatprotein 202 8693 WD40 0.11 0.80 0.25 0.14 0.18 0.53 0.31 repeat protein203 9170 WD40 0.16 0.11 0.05 0.05 repeat protein 204 9408 WD40 0.33 0.050.41 0.15 0.14 0.41 0.33 repeat protein 205 9522 WD40 0.11 0.18 repeatprotein 206 9734 WD40 0.11 0.05 0.11 0.15 0.07 0.25 0.11 repeat protein207 9815 WD40 0.11 0.18 0.14 repeat protein 208 10670 WD40 0.40 0.160.11 0.16 0.34 0.31 repeat protein 209 11297 WD40 0.53 0.15 0.16 0.05repeat protein 210 13098 WD40 0.19 0.11 0.54 0.31 0.14 0.26 1.85 0.14repeat protein 211 13172 WD40 0.04 repeat protein 212 13589 WD40 0.110.06 0.21 0.05 0.37 repeat protein 213 13608 WD40 0.11 0.04 0.59 0.33repeat protein 214 14299 WD40 0.16 0.05 1.09 0.38 repeat protein 21514498 WD40 0.21 0.44 0.30 repeat protein 216 14548 WD40 0.16 0.11 0.110.82 repeat protein 217 14610 WD40 0.16 0.27 repeat protein 218 16090WD40 0.43 0.04 0.37 0.85 repeat protein 219 16722 WD40 0.10 repeatprotein 220 16785 WD40 0.05 0.13 0.38 0.50 repeat protein 221 17094 WD400.29 0.15 0.24 0.81 repeat protein 222 17527 WD40 0.04 0.10 repeatprotein 223 17591 WD40 0.14 0.10 repeat protein 224 17769 WD40 0.39repeat protein 225 18047 WD40 0.05 0.22 0.98 0.15 2.68 0.07 0.19 0.80repeat protein 226 18414 WD40 0.16 0.15 0.34 0.23 0.19 repeat protein227 18986 WD40 0.41 0.15 repeat protein 228 19479 WD40 0.05 0.28 0.32repeat protein 229 20144 WD40 0.43 0.29 0.05 repeat protein 230 22480WD40 0.15 0.27 repeat protein 231 23079 WD40 0.13 0.04 repeat protein232 26739 WD40 0.15 0.18 repeat protein 233 26951 WD40 0.21 0.20 repeatprotein 234 26529 WEE1-like 0.04 0.18 protein 237 888 WD40 0.11 0.18repeat protein 238 14166 Cyclin- 0.16 0.05 0.05 dependant kinaseinhibitor 239 3189 Cyclin- 0.06 dependant protein kinase 240 9356Histone 0.11 0.22 0.46 acetyltransferase 241 65 Histone 0.16 0.22 0.270.22 0.24 0.34 deacetylase 242 14197 Histone 0.16 0.33 0.05 deacetylase243 9081 Peptidyl- 0.11 0.05 0.29 0.26 0.69 prolyl cis-trans isomerase244 13417 Peptidyl- 0.06 0.59 prolyl cis-trans isomerase 245 5755 WD400.16 repeat protein 246 6670 WD40 0.14 0.05 repeat protein 247 7027 WD400.14 0.15 1.30 0.15 repeat protein 248 7276 WD40 0.14 0.11 0.05 repeatprotein 249 7390 WD40 0.31 0.14 0.11 0.44 1.29 0.38 repeat protein 25012648 WD40 0.05 0.06 0.05 0.94 repeat protein 251 13171 WD40 0.19 0.630.19 0.34 repeat protein Table 13, the following numbers 1-12 representthe following tissues: 1 is bud reproductive; 2 is bud vegetative; 3 iscallus; 4 is cambium; 5 is meristem vegetative; 6 is phloem; 7 isreproductive female; 8 is reproductive male; 9 is root; 10 is vascular;11 is whole; and 12 is xylem.

TABLE 14 Oligo Table. Oligo SEQ ID Oligo ID Microarray Oligo Seq 521Euc_003910_O_4GATTTTAAGTAACTCAATTAGCAGTTCCAACATTAAACCATTATTATTACCCCTTTTATC 522Euc_019213_O_1CTCAAAAAGTACTTGGATGCGTGCGGTGACAACGGACTCGAACCGTACACTGTCAAATCT 523Euc_036800_O_4TTGTCAAGTTGCAGGACGTAGTGCACAGTGAGAGGCGTCTATATCTAGTTTTTGAGTACT 524Euc_040260_O_1GAAGAAATTATATAACTAGATACAAGGTTAGCTAGGTATATAATAGCGGTACAAGTCTTT 525Euc_041965_O_1GGACAAATCAAGTAGAACTTCTCTCGGCAGCATCAGTTTTTCTAATCCATGCCTTGTTGC 526Euc_002906_O_1CTCAGTTCTGATAATGCCTCGGATATATGGCCGAGTGTTCGCTGGACGGCCTCTTATGTT 527Euc_001518_O_3GGAGATTCTGAACTGCAACAGCTCCTACACATTTTCAGACTGTTGGGTACTCCAAATGAA 528Euc_008078_O_2GACTGGTAAAATCGTTGCACTAAAAAAGGTCCGGTTTGACAACTTGGAACCTGAAAGCGT 529Euc_009826_O_4AAACACCAATCTATCAACACTGTCGAGTTTAGTCACTAGTAGAACCGGAGATAACAAACA 530Euc_010364_O_1CTATGATCCTGAGCGCAAGCAAGTTATGACCAATAGAGTCGTTACACTATGGTACCGAGC 531Euc_011523_O_1TGTTGTGAAGGTAGTTATAGCCATCGATTAGACAGTGATTAAAGTAGTACCCGTGCCAAT 532Euc_024358_O_2CCACATACAAGAGTTGTTACGCTACACATCCTATACCATCAAAGGAACGTTGGAATGCCA 533Euc_039125_O_3TATGATCGACACAAGCATTTTGTGTTGGAGCCTCAGCTAATTGTATGTCATCGAGTACTT 534Euc_005362_O_3AAAATTTTTGCTACGGATAATGTTGTGAGGCGAGGCAGTCGAAATTACGGAGGTTGACTT 535Euc_044857_O_1ATGCAGGGATCAAATTTGTGAGTACTACGTAAAATTTTGCTACGGAGGCGAGGCAGTCGA 536Euc_001743_O_1GAAGAATACAGGCTCGTACCTGATACACTGTACCTGACTGTTAACTACATAGATCGGTAT 537Euc_012405_O_1TCCACCCTAAATGCGATACGTGAAAAGTATAGACAACAGAAGGTAAACTATTCATTACTG 538Euc_003739_O_2AGGCTTCTAGTTGCGTTCCCCCAAACTACATGGATCGGCAGCAGGATATTAATGAGCGGA 539Euc_022338_O_2GAGAAAAATGACAGATTGATATCGATGATGATGACTGTCGTGTCATCAGTAGTGTGCTTT 540Euc_028605_O_5TTTCCAATTGTAGTTCGTCTTTTATTGTAACAATAAATTGATAGATACTGATTCGAAATA 541Euc_041006_O_1ACATTTATGCTAACTATAGGAGAACGGAGAATTGTAGCTGCGTCTCTGCTAACTACATGG 542Euc_006643_O_1TTCTGGCTTAAAGGCTATTCTTTGTGCACAATGACCTGAGGGAGGTCTCGACAGACCACT 543Euc_045338_O_1TTCATCCGGGTCCTGGTTATCATACTCTTATATATGTTGGGGAATAACGGTTCATATGTT 544Euc_046486_O_3GGGTGTGCTTAATAGTTCTTATTAGTCTTAGCTTATTATCTTTGATTGGACATGCTATAA 545Euc_012070_O_2CTTGCTAAGTAGACATGTTATATTTCTAATGCTTTGAGAACAATATTACAGTATAATTAG 546Euc_006617_O_2AATCATCGACTAGACCGATGGTCAAAGTGGTAATCATGTAATTAAACGCGTTTGTCATTG 547Euc_007827_O_2ATGGAAAAATCTATGGATATGAAGGATTGAAGATATCCGTCTGGGTAAGCTGTGTATCAT 548Euc_008036_O_3TTATGATTTGAGAAAACCCTTGCAGGCTGCGATTTGCGGATCATGACAGCATAGTTTTGC 549Euc_001596_O_2GTTTTGTTGTGAGGGCTTGGTAGGTTTTCATTATATTGTAATGTCGACGACAGAGATTTT 550Euc_005870_O_3CCAATTAATGTTACTGCTCAAGCTGACGTACCTGCGAAAAAAGCACCAGTGACTGCTAAT 551Euc_006901_O_3TGATGTCAAAACGTAGCTCTTTTTTGTGTGAGCTATCCTGCTAAATTAAACCTCAGCAAA 552Euc_006902_O_1ACATGAGTATTATGAATACTTCGGTCCTGACTATACACTTCATGTTGCTCCGAGTAACAT 553Euc_007440_O_2GAATTGGCGATCACAATCTACTGTAGTCAATACTCAAGTGGGAGGTGTAAATAGATTCCA 554Euc_008994_O_1GATCATGTGTAATCAGTATATCAGGTTAGAAACAGTACTCTTGAGCTTAGCGGGCACTGT 555Euc_024580_O_2TCCTGTGAAGGTGGTCGACTCAATCAAAAGGTACCTTGTAGATAAGGTACCTTTTCTCAA 556Euc_037831_O_5GCATTTTATACGACGGATAGAGTCATGACCGTATCTTTCCATAAGTTTGGGGACTTCTTC 557Euc_034958_O_3CCTCGTTTCTTTGCGGTTCGGACGCATCATGGATGTATCTCCAAAGAGTAATCTGTCGAT 558Euc_022967_O_2AATTCAGATCTATTAGTGAAAGTTGGCATGAGTCTCAATCTTAGGGGAATACAGTACGGA 559Euc_008599_O_3TGATATGAGTATCATAACTCGGATGGTGACAACTTTGTACTACGGTCGGCACCGGTAGAT 560Euc_009919_O_1CATATACAATCTTAGTGGATTAGCTGAGGTCGAAACTGACAAGAGTGATCGCCCGTTGGA 561Euc_015820_O_2CATGGCTAACGCTGGCCCTAGCACTAATGGGAGCCAATTTTTCATATGCACTGTAAAGAC 562Euc_008327_O_2AACAAAGTCTACCTTGACATTAGCATCGGTAACCCTGTCGGGAAACTAGTCGGAAGAATT 563Euc_004604_O_2TGTGCTTGGATATACTGTATAAGCATTCTATATTATGCTTGTTGGCTTCGTTTTGAGGGA 564Euc_000966_O_1TTAACGTCGACCGCTTCTCTGCCCCTTGAATTTTCCCGAGAAAACCAGGAACCTGCCAAA 565Euc_001037_O_1TGTTGAATACGATGTATTATAATGTTGGTGTCTTGGTGAAATACAGAATTATGCTTGCGT 566Euc_004603_O_2ATCGCTGTGGCTGATCTCGTCGCTCCGGCTTTTCATAAAAATCATGGCTGAGGCAATCGA 567Euc_005465_O_2CTCGCAACCCTATATCTCGCTCAGGCGAAGAAGTCTGAGGATTTGAAAGAGGTGACTCAC 568Euc_006571_O_1TGTTTTTGGGTACACGCAGTTAGGATAACTAGCATGAAAGCCCGATCCCGCATATACAGG 569Euc_006786_O_2GAGGACTAGCCGGAACTTCATCGAACTCTCTCGGAGGGGTTACTACGATAACGTCAAGTT 570Euc_007057_O_1GATGGCTAGCACTGTGTAGAAAGGTGAATTTAAAGTACTTGTCTACACTGCTTATTAAAT 571Euc_008670_O_2TGAGACTGTCTTGGCGTGTATTTTGGAATAAACTATTATCACGTTTTGTTAAATATAATA 572Euc_009137_O_3TTACAAAATGGCTCTCAGAAAGTATCGAAAGGCCCTGCGCTATCTGGATATCTGCTGGGA 573Euc_010285_O_2AATTTTATGTTTGCTACTGCTTAGTGCTTAATGGACTTGCGTAGGTATTCAAATTACAGA 574Euc_010600_O_1TGGAACCGTGGTATCGGCTGACGTTATCCGTGATTTTAAGACTGGAGATAGTTTATGCTA 575Euc_011551_O_2CTTTGATGTATCCTCAGTGTACTGCTTTTAGCTATGTATAGATCGAGTCAACTCATTGAA 576Euc_020743_O_3TTTTTATTATTTACCTTCGCCTTTACGCTGCATACGTTAATAGGTTATTATTTCCTTCAA 577Euc_023739_O_1ATTTGTCCATGACAATCGTAGTCGAAGACACGATACGCTCTTAGATGGTACGGAAATCTG 578Euc_031985_O_2TGAATAGAGATAACTTTTCTGAGTGTGAATTGGATATTACGTTGCAAATAGCCGAATGAA 579Euc_032025_O_2GCTTTAGGTTAGGGATCCCTGTAAGCTGATGATAGATATTGGAGATGGTACTTGTAAGAT 580Euc_032173_O_1TGTTGTGTTTGGAAAGGTGCTGTCTGGGATGGATGTTGTCCACAAGATTGAGGCTGAAGG 581Euc_009143_O_1GGAAAGCGGGGAATGAGCATGTGGATATTATCTCTTTCTACAATGAAATATTCATTCCTT 582Euc_000349_O_1CATCAGGACGTTGACTCTAATTAAGACATATGTGACAGAGCGCCCTGTTAATGCGGTTAC 583Euc_000575_O_2CTTTAGGTTTGATCTGTCTGTTTTGTCTATCCTGCGAGTTTCGAGCATGTGCGTGTGTGA 584Euc_000804_O_1CAGCCCCAATAGATACTGGCTCTGTGCCGCTACTGAGAACAGTATTAAAATCTGGGACCT 585Euc_000805_O_2AAGAATGAAGCTGATATGAGTGATGGAACTACGGGGGCCATGAGCTCAAATAAGAAGGTC 586Euc_000806_O_1TGACTACAATTAGCACCTCACCATTATCGAACTGTATAATTGTGCTTGCCTGCTATTATT 587Euc_002248_O_4TTGAAGCGGAAATATATATTTATGCTACTACATAAGTAATGTACTACTTGACAAGATGAG 588Euc_003203_O_1TACTCGATGTGGTATAGAATTTATCCAATGTACTCCTAAATGTAGATACATCGTGTATTG 589Euc_003209_O_2GCTTCGTCTGATACCACTATCAAGATAATAGGCGTGAGCAATAGCTCTGGATCACAGCAC 590Euc_004429_O_4GGTCGGCTTGCTAGTGTATCTGATGACAAGAGCATATCACTCTATGATTACTCATGAAGG 591Euc_004607_O_3GAAAGGAGAAAAGCATGGAGATCGATCTCGGAAACCTCGCATTCGACGTCGATTTTCATC 592Euc_004682_O_1GATTCAGTACCCGGATTCGCAAGTCAACCGGTTGGAGATAACTCCACATAAGCGGTACCT 593Euc_005786_O_1TTCCATGTATCAAGCCGCATCAATGTTTGTCGCTGCAATTAACATGTGTGCAGTCGATCC 594Euc_005887_O_2TTCAGCGCATTGTGTAAATGTAGATAGGTGATATATTTCTCGTTGCAATGTAGGGTAAGA 595Euc_005981_O_2TCCAATAATCACATTTACCATCAACAGGCATCAGCAACATACTGTTGTAGTGTAATTAAT 596Euc_006766_O_1GGGCATTCTGACTACCTGCACTGTATAGCTGCACGGAACTCTTCTAGTCAGATTATAACA 597Euc_006769_O_1AATCGTCTGGTAGATTGTCAAAAACTAATAAACCTGTGATTGATCCGGATTCTAGTAATG 598Euc_006907_O_2AGTTGAGGATTCTCCACTATGACAGCTCTCATGGCTTGAATCTAAAGTCATCTGGTTTTC 599Euc_007518_O_1GAACAATCATTCTGTAGAACACTAGAGTCTATATGCTTGACTGTATCGGTTAATTAATTC 600Euc_007717_O_1AGATAGCGATAGAGTTATACTGCATGTACTGAGGTAAATGTTTTGATTACTCCACCCAAT 601Euc_007718_O_1AAGAATTGTTAGGAGGTGTATACTTTCTGTAACTGTATTCAATGAGCATACACCTGACGG 602Euc_007741_O_2CAACTCATATAATGACTGGATTCTGGCAACCGCGTCTTCAGACACAACAGTTGGACTATT 603Euc_007884_O_1AGTGTAAAAGGATGCCCCTAATAGATTATATGCCAAGTGTAGTATATATAATAGTGCTTT 604Euc_008258_O_2AAGAATCTACAGTTGTCTTATGCTACTCTATTACTCAATTATGCTGTGCTATTGATTGAG 605Euc_008465_O_4TCTGAATACATACTTTGTGGTCTCTATAAAAGACCAATGATACAGGCATGGTCATTAATT 606Euc_008616_O_5TAAATCTTCTCATGTGCCTGGCGTAAATTTTGCAGTTATTACTAGACCAAGATAGTTTCA 607Euc_008690_O_4ACATGGATTCGATCAATCGCCACATGACAACTAAAACAAGCGGTTCACGTGATTGTAATT 608Euc_008708_O_4AGATGAGTATGCTCGGGTGTATGATATTCGCAATTACAAGTGGAATGGATCGCATAATTT 609Euc_008850_O_5TCTTTGATTCTGTTGTATGGTGTATCTTATTGTATCTTCTATCTGCCCCCCATGTAATTC 610Euc_009072_O_1TTCGTTGTGTAGTACTGGGAGTTACTACTTGTATGTATGTAAATCATGTGGCGTCTGTCC 611Euc_009465_O_1GGAGATGTGTAATATGTCTGAGCGGTCACACTCTAGCTGTTACATGCGTAAAGTGGGGAG 612Euc_009472_O_3CCACCGTTGCGTAACTCGAATAGCCGGATTTTCGTTTTCGTTTTTATTTCCCCGTTAATT 613Euc_009550_O_1TGAGATGCTCTGTGTGAGGACTTTTACGAAACTTGAATGGCCCGTAAGGACAATAAGCTT 614Euc_010284_O_3TGGGTTGTTGCGACGGGTTCTACAGATAAGACTGTTAAGTTATTTGATCTACGCAAGATC 615Euc_010595_O_1GCAGAGGTGCCTACATATGCTTTAGAATGCTAGTAGCTTGGAAGTGCAACACGCTCGTGA 616Euc_010657_O_1AGTAAAGTTTAACGACTATGCATCTGTCGTAGTATCAGCCGGCTATGATCGTTCAGTGCG 617Euc_012636_O_2CGTTAGGATAGTCTTTAAAGGAGTTGGTGATTATTGATTTCCACCCAATATATGTAGCGT 618Euc_012748_O_2GAGCAAGCTACTTACAAAAATCGACAGCGTCTTTACCTATCTGAACAGACAGATGGCAGT 619Euc_012879_O_2TCCTTCCGACAAGTACCGTATTGCAAGTTGTGGTATGGACAATACGGTTAAAATCTGGTC 620Euc_015515_O_1TTTCACTCGATGACGGTTGGCCGGATAAATAATCGCTTATATAGTCCTAATAAGTTCCAT 621Euc_015724_O_3ATATGTAGGTGGTAGAGGTGTGGATATTGCATAGACCGAACCTCCGCAGGTCCGCATTCT 622Euc_016167_O_1CCATTGAACTACTTATGGATTACTTTATACATGAAATATCATGCCGGAGTAATTTTGAGT 623Euc_016633_O_3AGCATTAGAGACCTGGATTTTAGTCTAGATTCAGAGTTTTTGGCTACGACATCTACTGAT 624Euc_017485_O_3AAAGGTTTATCCCTCATTGGATTTGATATATAAACTGAGAGTGTTTTGCCCCCCATTAAA 625Euc_018007_O_1GTACAGCGTGTATTTCTTGTTACGATACTTGAGGGGTTAGAGGCACCTACGAATTAGGAA 626Euc_020775_O_3ATATCCTTATGAATGAAGTTTGGATGATAAGTGGCGCCAGACTTTCTACTCACCCTTTTT 627Euc_023132_O_3TGATCACATCGTTGTTTGCAATAAGACGTCATCAATTTATATCATGACTCTACAGGGACA 628Euc_023569_O_2TTTTCCCAGTGTACTGCGAGAGTGATGCTACATAAGTTTACTCTTGTGTCTAACTTTTCC 629Euc_023611_O_1AGATTCTACAGATGGCGCTATACGAGCTGTTATACGGACATTTTATGACCATACACATCC 630Euc_024934_O_3TGCTACGGGAAACCAGGACAAAACTTGTAGGATTTGGGACATACGAAACTTATCTAAGTC 631Euc_025546_O_1CAAGTCATATAGTTACAGTGTCGCATGACAGAACAATTAAGCTCTGGACTAGTAACGACG 632Euc_030134_O_2TGCCACATCGTAACCATCATAGCACTTATCATCTAATTATGGTGAAAGGGAGTTATATAT 633Euc_031787_O_5GTTTATACTTATAAACAACAGAGAGACAACTGTACAGGTGTTGTAAACACTCCCAGTGTG 634Euc_034435_O_1CTGTGTTTTAGCCCGAGGGCCAATCACTTAGTTGCTACTTCGTGGGATAATCAGGTACGG 635Euc_034452_O_3GCAAAGTAGAGTTTAAGTTTCGTTGTGCTTGGACCGGAAAACTCACATGCTTAGAGTTTA 636Euc_035789_O_5AAGATTTGGGCATAACTTGTATGAACTTTTTCTGTTGTCGACACTGTAATTACACGAGCT 637Euc_035804_O_4AAACAGATGCATGTATGCTTCATAACTCTATAGATATGGAAATGTCACTGTACACTGATC 638Euc_043057_O_2TTATTGGTGCACAGGACGGAAAATTGCGCATATATTCTATTTCAGGTGATACATTAACAG 639Euc_046741_O_1AGGCACAGACACTTGCCTAAACCAATATACAAGGCAGGTATTCTAAGGCGCACCGTGAAT 640Euc_047161_O_4CATGCGAAGGTTTCTGGGAATTTTCAGTAGAAAATTCGGTCGTGGCGGCCATCCTCGATA 641Pra_001766_O_1TTAAGCTGATAGCTTTAGTTCCTACGTGGAATGTATAAATGCACCATTGTCCATAAGGCA 642Pra_002927_O_2GGATGCTCTGGTTACATGACTACTCCTTAGGGAATCAGTCAGACATTTTAAATAACTTCC 643Pra_007642_O_2TCATTAAGCGGTACTGGCAGAGGACATGTCTATTTATACAAGCAAATGGTCCTATTGGCT 644Pra_013714_O_1ATGTTGGTCAGACCTCAAATATTGTACTCCCCACACTAGGGAGCATTTACGGTGAATATA 645Pra_016332_O_1TCCTCTCGACCCTTAGAGTCCTCTGCGAATCTTGTTGTTAGTTACTGTGTACGCTGTAAC 646Pra_021677_O_3AAGCATGTTTTGAATTTATGGTGGTGGCATGTGGATATTTGAACTTGGTTGAGAAAAATT 647Pra_027562_O_2CATTCCTATTGAAGGGTCAACCTTTAATTTTGGCTAGCAGGACTGTATAGGATTATATGC 648Pra_001504_O_2TTATTGTATTTTAGATTCTTGATGGCCATCTAAACTTCTGGCTGCTTGGTGCAACATTGA 649Pra_015211_O_2ATAGCTAATGATTCCATGCTATCCATGGTATCTACTTCACGATAATAAAGGTCTTAGTCC 650Pra_020421_O_2CACCTAATAGGCCTGAGTATTGCTCACCACTATGCTGATATGGGGAGCAATAACGTTAGT 651Pra_003187_O_2TTTCTTTTCACTTTGTACTAATGATCATTGTGACCACAAAATCTTTATACACAATACAGA 652Pra_015661_O_1CTTGTCACTATCCTCATATTGATATCACCTCGTGTATGTTGTGGGGTGGCAAAATTACTT 653Pra_013874_O_1TATTTTAACTCAGCGACTTACCAGCCTAGTAAGCAATGGGGAGCTTGCATGTATTAGTTT 654Pra_014615_O_1ATTCGTCCTGGTCCTTTAGGACATGTACTTATGTCCATGCAAGTGCTTCTTGCCTAAGCT 655Pra_004578_O_2TTCTAGGCGATATATATCGCCGTAACTTTGGATGTGTTAAGAATATAGGGGATCATTAGC 656Pra_023387_O_3AGTTGCAGAGTGTGTAGCAACTGATGAGCATAGTTGTTATGTTTCTCAACTCAGTTGCAC 657Pra_006970_O_1AAGAAACTCATACACTGGACAGGCCAACCTTCCAAATATGTGTTTAGAAAACCTTTGTCT 658Pra_010322_O_1AAGGGGTGCTATCCATATCTAGAATCTACCATGCTCAATGAGGTATCTTCATTAGTATAC 659Pra_022721_O_1ATCTAATGCTAGTTTATTGATTTCTATGATCCAAGACCTCGTCATAGATCAAGTGCCTAG 660Pra_023407_O_1TTGTTATTAAATACCATTCAATATGCTTATGATTCATGAATGCTTAAGAGATTCTGCTGC 661Pra_001945_O_2GCTTCTAAACTGTAGAAGCCTGTTATCTTTAGACTCGTGGTTATGTGAACTACTTTTACA 662Pra_008233_O_1GGCTGTGGGGATTCGAGCCTGATGGTTATGCACTGTGGCCAGCAAGATGTTGAAGTTTTA 663Pra_008234_O_4GCCTGATGGTTATGCACTGTAAGTGATCTGATTTGATTAACTATTTTATCAATTAATTTT 664Pra_022054_O_2ATGGTCATTATCCGAGATAGTGCGCTTTGTCATGGGAAAATGACTATTGAATGTGAGTTT 665Pra_012137_O_2TTTTCTGGTGCATCCTTAACACAGCTTGGTTACATGGTGAATTACAGTATTTGAAGGAGT 666Pra_012582_O_2AGATTTAATGCCACTTAGGTGATCGGTGACCCACTTGTACATATAGATGTTGGCGATGTT 667Pra_015285_O_2AAGAAATTCATCAATTCTTTGAAATTATTGTTCCCTTTTGATGCGGCCCCTTTCTGGAGG 668Pra_017229_O_1TAAAGTATATTTTAGCCGCTGTTGTTGTAAATTTATGTTTTTCATTGCTATCAACATTTA 669Pra_020724_O_2GGTTTTCCTATAAGATGTATGAATTCGCACTGTGGTGCAATTTTATGAATTAAACTCAAA 670Pra_004555_O_1TTTACTATTCCGTCTGGGCTTAGAGATGTACGTTAATTGGTCATTTAAGACGACTCAGTT 671Pra_004556_O_5TCAAATCTAGTCAATATCCGTGTTGAGCTAAACAAGCGCTGAAAGTTTGCTCGAATCAGC 672Pra_005729_O_2AGAAAGTTGTGTACTAATTTGTATTGTAACGTCCATTTATCCAACGAGTCCTCCATTCAT 673Pra_007395_O_3CAGTACTGTATTCGAAGATCCTGAAAATTTACTAAAACAAATGGAATATCAACAACCTAG 674Pra_009503_O_1TTGCTCTATATAATTTGTGCTCGTGTGTGTACTTGAAGATCCATCCTCACATAGTCCAAT 675Pra_011283_O_1GTGTGTATAGTTTTATAACACTCTATGGTATCACTACCACTATGGGCCTGTTTAGTCCAA 676Pra_012322_O_3GAAGCAGAATCAGCTTTGACCAGTATTTAGTGTCTTGTATACAATTCTTGTTTCAGTGAA 677Pra_023236_O_3AAATCAAGATTAAAATCCGAAACCAAGGCTAACCAGCAAACTGTGAGGTGTACATTGTTG 678Pra_000171_O_2TTCCAAGCAGAAGGGCACATGTTGTGACATCAAGTAGTAGATTGTTCTGCAGATTCTGGT 679Pra_000172_O_1GTTAATGTAATACATTTAGTTTTTAGATAACTGTTAATGTGTAGTAAAGCACTAGGAAGA 680Pra_001480_O_3GAGGCTTCAAAGGTTTTTGTGTCTTTTCTAGTTATTATAAACGCTTCATAGGTTCCTAGG 681Pra_001692_O_2GAAGATTGTAAGTTGGGTGAACTTTTTTACCACGCTAGGTTGATCTATTTTAAGACTCTT 682Pra_005313_ORF_O1AAAATAGCTGCGCGTACCACAAAGGTGACAAACGCCGGATTTCTCTTATCAGACTTGTCA 683Pra_006362_O_1TTTAATTATCATAGTTTTATTCCGGCTATCTTGATCATTCACGGAAGTCCCGAGAGTCAA 684Pra_006493_O_3GTGGAGTGAACGTGGTTACTTCAATGGATTACCCTTCTATCGTGTCATTAAACACTTTGT 685Pra_006983_O_1GCTAACTCTTCTAGTTGAGATCTCCATCAATTAATGGATACAAACATTGAGTTTCACTTT 686Pra_007665_O_1GGATCACTACTGGATTCCGTTACATTAGTTATTGCAAGTTGGTTATTATGTACGTTTATA 687Pra_012196_O_1ATGAACAAATGCAATTACCCTGTTTTATTCTATCCCGCTTTAATTAATATTGGTCATGTT 688Pra_013382_O_1TTTGCTTGTGGATTGTACTGTGGTACATGGTATAAATCTATAGGCTATGTCGATTATTTT 689Pra_016461_O_1ATATAAGATATAAGATATTGCCAGCAAACTATTTGACAGGTTATTTAATAAAGTGTGCTA 690Pra_017611_O_1TTTTAAATGTGGACAGAGGCACTATAAGAATGCGAAATATCGTCGGAGCACGACTAATTG 691Pra_019776_O_1ATAGACTAGTTCTACAAAGCCCTAGGATGATGGACTTCATTTCTTTTGCATTAAGATGAA 692Pra_020659_O_1GATTTCTTATGGGGTTGGAACATTCCTCGCTGCCTTCTGGTAATATTAGGTTATGCGTTT 693Pra_022559_O_3AATTGAGGTTGACTGTGTACTTCTCCAGTGGACAGGAGAAAGCGATAAAATTCAAACGTT 694Pra_024188_O_5AAGGAAGGGCAAATAGAGCTCGCGCTCAAGAAATACCTTAAATCGATACGGTATTTGGAT 695Pra_027973_O_2TAATTTAAGAGCTATGAAACAACTACCTTTTGGAATGGTTTTGTTTTTAGCATCCCAATT 696Pra_001353_O_1TTGTAAATTATGCTGGTTCCATATGGGGGTTAATCAGTATCCTGGTTATTTGTGACACCA 697Pra_001978_O_3GTTGTGAACTATCAATAGACGGGGATGGTCCTTTTTAGCTGCTCCTTAAGCAGCTCAAAT 698Pra_002810_O_2TCAATTCCGGTCATATGTAGACGACTATAATGTTGTTTGTGTCCTATAACTATAGTGTTG 699Pra_002811_O_1CATTTTACACCCTATAACAAAATATAGTGTCATAAGTTTACACCAGGTAACAACTCTATA 700Pra_002812_O_3ATGGAGAGTTTTATTCATTACATGAAAGAGTATGTCACCTTTCGTGCTCCATCTATTGAT 701Pra_003514_O_1TTTCACGTCCTGTATACTCACTCAAGCAACTTTAGGATGAAGAGCTAAAGTATATCAAAG 702Pra_004104_O_2AATGCACTCTTTATAAAGTGGGATGAGGTATGTGTTTCCTTCCTATTGGCTAACCTGAAT 703Pra_005595_O_1ATTGGGCAATCGTTATTGATTTTACCTATCGCTATCTCACTGTCCGCCAATTTAGTGTAA 704Pra_005754_O_1TTTCAGCGGATATAAAGTCTTCCAACTTGTAAACCGGTGCTGTGAAGATTAAAAGTCCTT 705Pra_006463_O_1GCTTTAGAGGCAATGGTAGATTATGAAGTCAACACCAGGGAGTTTGACCGTTTGGGACAT 706Pra_006665_O_1CATTCAATTTGACATTGGAGTTTCAAGGCATTCCAAGGATAGCATGTACACAAGTTGAAT 707Pra_006750_O_1CATAAAATTACTATGGAAGTTGGATCATTATCTATGCCATAGTGGAGTAGAACTAGATTT 708Pra_007030_O_1CTCTTGATTCTAGAATCTAAACTACTACCTTGCGGACATGACTGAGCATCTCTCTAACAG 709Pra_007854_O_1CAGGGTTGTGCTAGTTTAACATTTTAACTTAATGTAATCATGTAAGCTTTAGAGAGGTGG 710Pra_007917_O_1GTAAATGTTTACATTGAGGTCATGCATGAGTGTTAATTACGCTTTCACTACTGTTCACTT 711Pra_007989_ORF_O2AATTAAAGCTTGGTTGTATGATCATTTGGGATCGAGAGTAGATTATGATGCTCCTGGGCA 712Pra_008506_O_1TTATCTAGCTAGAAGTTGTGAAATTAAGAGGGATGTGAGGATTGGGTTATAACTAGTGTA 713Pra_008692_ORF_O2AATGAATCAGGCATTAAAGCGGGAATCATTTATGACTTGGCAACCTGAAAATTCTATTAA 714Pra_008693_O_2TTCTTGACGTTTTAATATGGTATGGTATTAAATTTGGAAGGCCTATTCGATTGTTTGCAA 715Pra_009170_O_1TTCTTATAACCTGTACGATTGCCGATATATCACCAATTTTGCTGATTTTAATCTGAGTTT 716Pra_009408_O_1CAATTTCATATTCGGGTTCAATGTAGTGCCTCTCATTTTAGGGTGATAGCATGAGTTTTT 717Pra_009522_O_1TCCACAAGTTAACATAGGTAACTATCGACTGAAGTGAACTGGGGGGCAGAAGCTAACTAT 718Pra_009734_O_2TTTAGATAGCCATTTACATTTTACTTATTATTGGACTTGTAAAGATTTTTGTACCCTTGT 719Pra_009815_O_4TTGCTGAAATATTTCAAGCTGAAAGTTATGATTCTGGCCAAGAAGTCTACTGAAAATTTG 720Pra_010670_O_2AAACATAAGTTTGGCCCAGATTCGGTTTATCATAAAATCTGGCTGCATATAAGGTGTCAG 721Pra_011297_O_1ATGTTCTAGAATTTGTCTAAGCTAGCTACTGGTGTTTAACTGATATGGAAAACTTTTGCC 722Pra_013098_O_2TTTGGGGAGTACTTTAGTCAATAAAAGTGAAGTGAATCATGATATAAAGGGTTTAAGTAA 723Pra_013172_O_2AGAAGTTACTAATTTGTAGATAAATTCTAACGAAGGTGATGATAGCATACACGTAATGAA 724Pra_013589_O_2GAATTTTGATGGTAGCGTATGGTTGAAGGAAAACTTGGATATATCATGTAAACATTTTTC 725Pra_013608_O_1TTAATGAACCGCTTTTTCCTTGAGAGGCTATGAATGCCTGTAGAACTAATCCTTTAAGTA 726Pra_014299_O_2TTTCTCTAACACTATATTTTCTGGTATGACCGCTCTACATTGTATATTAACCCTTGCAAA 727Pra_014498_O_1TATATTCACTGTGCTGGGATTATCCTCTCCCCTTTTTGACCCACTGTTGTGTGTATTTGA 728Pra_014548_O_1GAGCATACAGCGTTATCTTTGAGACGAGTCATCAATGATAATATCCTCGTAAAAGGTTAC 729Pra_014610_O_2TTTATTCAATTACGACGGATTCAGTTGGCCTTTTGTAACATTCAAGTATCCATCTATCAC 730Pra_016090_O_2ATGTTCAGGGGTATTAAAAATTCAGAGGATAAATTTCCTCACTCTCAAGTGTTAGATGGT 731Pra_016722_O_2CAAAGTCTAGACGTTAATGTTTTGGAACTCTTTTTTCGAATTTGTGCCTATTGAATCACT 732Pra_016785_O_3TATAAATATATTGTACTGGGGATCCAAGACATGGCAATATATGTCGAGATTTTCATTTTC 733Pra_017094_O_3CTTTTGCATGAGTTCAAATGTCTTTGTGACATATTGTCTTGAACCACCGAGGATATATCA 734Pra_017527_O_2GTTTGTATGTCCAATAGATTATAACCTATTTACTGTGACACTATTCTTCACACCCATGTC 735Pra_017591_ORF_O2AGATCTAGTTGTTTCAGCATCGTTGGACCAAACTGTTCGTGTATGGGATATAAGTGGCCT 736Pra_017769_O_2TGCCGTATCAAAAGATTGGTACTTCCTTATGGACACACAAGATCGTAAGCATGGCTGAAT 737Pra_018047_O_2TTGATGGCCACATGAGTTGTTTATACAAGTCGTTGTTTTATGAGAGAACCTTCTTCAGAT 738Pra_018414_O_1ATTTCTATAGTGCCATATGCTTGTCGGTTGTCATTGACCTCTAATAGAATAGCCAGAGTA 739Pra_018986_O_1TTCACGGCAGTTGAACTAGTCATAGTGGAATATTATTTAAATGGTGTATTCTAGTCACAT 740Pra_019479_ORF_O1TGCAGGCGCTCTATAGTTCTGTTCTCTAGCATGAAGTGTGTATTTTATCTATTGTGGACC 741Pra_020144_O_1TGTCTTTAATCTTCAGGGTTCGTTACTAACAATTGAGCTCAAATCTCTATTCTGACCAGC 742Pra_022480_O_1CATTTATAGAGTTGTGCAAAATCACCCATAATGCTATGAATTGACAGGTGACTGTAATCT 743Pra_023079_O_2GGAGAAAATTTCCTATCCCTTTGTGGGTGTGTGAAAAACGAAATATAGAGGAACAATGTG 744Pra_026739_O_2ACCAATCATTTATTTGCAGTGTAGTTGATATGAAGGGAGAAATATGACAGTTGGTTTCAA 745Pra_026951_O_2AAGTTAATGTTCTCATAGGTTATTCATTGGAGTTGTCTCGTATGTACGCTGTGCCGTAGT 746Pra_026529_O_2CTCATAAATTGAGGCTTGCCTACGTTAATTGTTATATATGGAGAGCCATGCTAATTGTTA 747Euc_006366_O_2GCAGATCATGTAATTGTATCTCAAATTATAGTATCCGTATTCTGTACAAATGCTCCGGAA 748Euc_017378_O_1TCTTTACGCAGATGGTGACTGAAGCTGGTTCCGAGATCGGCATATGTAGCTGGTAGAGGT 749Pra_000888_O_1TTCACATTGAGGGTTGCCGTCGGTATTCGCCGATGATATCCTGTTTTACGCGCAACAGTT 750Pra_014166_O_1TCATTATTTAGGGTGCAGGCTGTATAAAATGTTGTAAATTGTAGTATCAATGTGTACAAT 751Pra_003189_O_1GCATTCACCACGACAGTAAAGTAATCATTATGATTACTAATGTATTGCTTTCATGGGGTG 752Pra_009356_O_4AAAGGGTATATTTTGTCTCATGTTGGGGTGATAATTCTCCCTGAAAGTCTCCAAAATATA 753Pra_000065_ORF_O_2AAATTTCCGGTTGCCATAGTCTAGTGGGGTGAGGGTTCATTCTAGGGGATTTATTGTGTT 754Pra_014197_ORF_O1GCAGTGATAAAGGTACTTCTTGGTGATAATCCTAAAGCCTTACCCATGGATATCCAGCCT 755Pra_009081_O_2TTCTTTAACAAGGTAAAAATCCCCCCCTTGGCATGTAGCTCAATTAGTTGTAATGGAACT 756Pra_013417_O_1AGTTGTAAACAGTGTAATAAGGAGCAGAAGTTGTGATAGCTTTTAGGAACGATAGACTTT 757Pra_005755_O_1TGAACCAATTCTTGTATATTAGATATGTAACATGTATGAATGTCCATAGAGCAGAGCTTT 758Pra_006670_O_2AGCCAGGCACGCTTAACTAAATTTCGTTTAGTTCACCATGACTATTCGTTGAACTTAATG 759Pra_007027_O_1CAAAACCCCTTGTAGGGTGGACTTCTGTTGTATCCAATTTTTATGGCATAATTAGCTAGT 760Pra_007276_O_1AATTTGGTGATTATTCCTTACCATATCGTACTGTACAGATACGGTAAGGTCGAAATATAT 761Pra_007390_ORF_O1CATGCCGTGATCGGTCGATTGCATTAAGTGCTGCAAGGATCAAATAGTGGCACTGTCATG 762Pra_012648_ORF_O1CAAACATAAATAAGGTTGCTACTTTAAAGGGACATACGGAACGAGTTACTGATGTGGCAT 763Pra_013171_O_2ATTTATGGATGAGGTACTCCTTATGAATATCTTCAAACTAAGAAATAACTATATATGCAA 764Euc_045414_O_2CTTGGTTTTTGTTGAGCTTTCTATTTCAAGCAATTTGTGATTGGGGGGTTCTGCATTCTT 765Euc_044328_O_2ATGTCTAAAGAGCCGTGATCTATGAGTAGATTAGAAACCGCCTTTTTAGTTGCAAACGCC 766Euc_015615_O_2TTGCAACAAGGTATACTTAGTCAGTCCTTGTTATGTATGTCTTTTGTCAACCCTTCAGGG 767Euc_017239_O_3GGCGGAATCCCTTTGTTCTTTCGAGCTTTACGTGACAAGTCGGCCAGAAAGCAGTAGCAT 768Euc_018643_O_3TTGATGTACGAGCCGCTATATCTAATTCTGCCTCCCAGTCACTGCCAAGTTTTACTCTTC 769Euc_019127_O_5GTCTTGCATGTCAGCTATTATACAGTCCTGTTTATAGTCCTGTGATGTAATAAAAAGCTG 770Euc_022624_O_3AAGTAGGAGATCGTGTAGAGAGAATACTTTCTGCTCTCAGCGGCGAAGAGGTTTGTCTGC 771Euc_032424_O_1AATTGTGAGTAGAATAGGAGAAACTTTTGTACAAGATTAATACGTGTGGCATAATAAGAT 772Euc_037472_O_1TGATGTGCAGTTTACATTATTATGGTTCGAGTATTATTTAGCTGCCCTATCTTAAGTCAT

TABLE 15 Peptide Table. Patent Patent Protein ORF ORF SEQ ID TargetPatent PEPTIDE Sequence start stop 261 CDK type AMGDGSLGSGGRGNSGGGGGGGSRPEWLQQYDLIGKIGEGTYGLVFLARIKHPST 387 1820NRGKYIAIKKFKQSKDGDGVSPTAIREIMLLREISHENVVKLVNVHINPVDMSLYLAFDYADHDLYEIIRHHRDKVNQAINPYTVKSLLWQLLNGLNYLHSNWIIHRDLKPSNILVMGEGEEQGVVKIADFGLARVYQAPLKPLSDNGVVVTIWYRAPELLLGAKHYTSAVDMWAVGCIFAELLTLKPLFQGQEVKANPNPFQLDQLDKIFKVLGHPTQEKWPMLVNLPHWQSDVQHIQRHKYDDNALGNVVRLSSKNATFDLLSKMLEYDPQKRITAAQALEHEYFRMEPLPGRNALVPSSPGDKVNYPTRPVDTTTDIEGTTSLQPSQSASSGNAVPGNMPGPHVVTNRPMPRPMHMVGMQRVPASGMAGYNLNPSGMGGGMNPSGIPMQRGVANQAQQSRRKDPGMGMGGYPPQQKQRRF 262 CDK type AMEKYQQLAKIGEGTYGIVYKAKDKKSGELLALKKIRLEAEDEGIPSTAIREISL 99 1007LKQLQHPNIVRLYDVVHTEKKLTLVFEFLDQDLKKYLDACGDNGLEPYTVKSFLYQLLQGIAFCHEHRVLHRDLKPQNLLINMEGELKLADFGLARAFGIPVRNYTHEVVTLWYRAPDVLMGSRKYSTQVDIWSVGCIFAEMVNGRPLFPGSSEQDQLLRIFKTLGTPSLKTWPGMAELPDFKDNFPKYVVQSFKKICPKKLDKTGLDLLSRMLQYDPAKRISAEQAMGHPYFKDLKLRKPKAAGPGP 263 CDK type AMDQYEKIEKIGEGTYGVVYKAIDRSTNKTIALKKIRLEQEDEGVPSTAIREISL 120 1004LKEMQHGNIVKLQDVVHSERRLYLVFEYLDLDLKKHMDSCPEFSKDTHTIKMFLYQILRGISYCHSHRVLHRDLKPQNLLLDRRTNSLKLADFGLARAFGIPVRTFTHEVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFAEMVNRRPLFPGDSEIDELFKIFRIMGTPNEDSWPGVTSLPDFKSTFPKWASQDLKTVTPTVDPAGIDLLSKMLCMDPRRRITAKVALEHEYFKDVGVIP 264 CDK type AMVMKSKLDKYEKLEKLGEGTYGVVYKAQDKTTKEIYALKKIRLESEDEGIPSTA 23 937IREIALLKELQHPNVVRIHDVIHTNKKLILVFEFVDYDLKKFLHNFDKGIDPKIVKSLLYQLVRGVAHCHQQKVLHRDLKPQNLLVSQEGILKLGDFGLARAFGIPVKNYTNEVVTLWYRAPDILLGSKNYSTSVDIWSIGCIFVEMLNQKPLFPGSSEQDQLKKIFKIMGTPDATKWPGIAELPDWKPENFEKYPGEPLNKVCPKMDPDGLDLLDKMLKCNPSERIAAKNAMSHPYFKDIPDNLKKLYN 265 CDK type AMDQYEKVEKIGEGTYGVVYKAIDRLTNETIALKKIRLEQEDEGVPSTAIREISL 149 1033LKEMQHGNIVRLQDVVHSENRLYLVFEYLDLDLKKHMDSSPDFAKDPRLVKIFLYQILRGIAYCHSHRVLHRDLKPQNLLIDRRTNALKLADFGLARAFGIPVRTFTHEVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFAEMVNQRPLFPGDSEIDELFKIFRILGTPNEDTWPGVTALPDFKSAFPKWPAKNLQDMVPGLNSAGIDLLSKMLCLDPSKRITARSALEHEYFKDIGFVP 266 CDK type B-1MEKYEKLEKVGEGTYGKVYKAKDKATGQLVALKKTRLEMDEEGVPPTALREVSL 199 1116LQLLSQSLYVVRLLSVEHVDGGSKRKPMLYLVFEYLDTDLKKFIDSHRKGPNPRPVPAATVQNFLYQLLKGVAHCHSHGVLHRDLKPQNLLVDKEKGILKIADLGLGRAFTVPLKSYTHEVVTLWYRAPEVLLGSAHYSIGVDMWSVGCIFAEMVRRQALFPGDSEFQQLLHIFRLLGTPTEKQWPGVTTLRDWHVYPQWEPQNLARAVPSLGPDGVDLLSKMLKYDPAERISAKAALDHPFFDSLDKSQF 267 CDK type B-2MERPATAAVSAMEAFEKLEKVGEGTYGKVYRAREKATGKIVALKKTRLHEDEEG 41 982VPPTTLREISILRMLSRDPHIVRLMDVKQGQNKEGKTVLYLVFEYMETDLKKYIRGFRSSGESIPVNIVKSLMYQLCKGVAFCHGHGVLHRDLKPHNLLMDKKTLTLKIADLGLARAFTVPIKKYTHEILTLWYRAPEVLLGATHYSTAVDMWSVGCIFAELVTKQALFPGDSELQQLLHIFRLLGTPNEKMWPGVSSLMNWHEYPQWKPQSLSTAVPNLDKDGLDLLSQMLHYEPSRRISAKAAMEHPYFDDVNKTCL 268 CDK type CMGCVLGREVSSGIVTESKGRDSSEVETSKRDDSVAAKVEGEGKAEEVRTEETQK 291 2042KEKVEDDQQSREQRRRSKPSTKLGNLPKHIRGEQVAAGWPSWLSDICGEALNGWIPRRANTFEKIDKIGQGTYSNVYKAKDLLTGKIVALKKVRFDNLEPESVRFMAREILILRHLDHPNVVKLEGLVTSRMSCSLYLVFEYMEHDLAGLAASPAIKFTEPQVKCYMHQLLSGLEHCHNRRVLHRDIKGSNLLIDNGGVLKIGDFGLASFYDPDHKHRMTSRVVTLWYRPPELLLGANDYGVGIDLWSAGCILAELLAGKPIMPGRTEVEQLHKIYKLCGSPSEEYWKKYKLPNATLFKPREPYRRCIRETFKDFPPSSLPLIETLLAIDPAERGTATDALQSEFFRTEPYACEPSSLPQYPPSKEMDAKKRDDEARRLRAASKGQADGSKKERTRDRRVRAVPAPEANAELQHNIDRRRLISHANAKSKSEKFPPPHQDGALGFPLGASHRFDPAVVPPDVPFTSTSFTSSKEHDQTWSGPLVDPPGAPRRKKHSAGGQRESSKLSMGTNKGRRADSHLKAYESKSIA 269 CDK type CMYSKSSAVDDSRESPKDRVSSSRRLSEVKTSRLDSSRRENGFRARDKVGDVSVM 107 2236LIDKKVNGSARFCDDQIEKKSDRLQKQRRERAEAAAAADHPGAGRVPKAVEGEQVAAGWPVWLSAVAGEAIKGWLPRRADTFEKLDKIGQGTYSSVYKARDVTNNKIVALKRVRFDNLDTESVKFMAREIHILRMLDHPNVIKLEGLITSRMSCSLYLVFEYMEHDLTGLASRPDVKFSEPQIKCYMKQLLSGLDHCHKHGVLHRDIKGSNLLIDNNGILKIADFGLASVFDPHQTAPLTSRVVTLWYRPPELLLGASRYGVEVDLWSTGCILGELYTGKPILPGKTEVEQLHKIFKLCGSPSDDYWRRLHLPHAAVFKPPQPYRRCVAEIFKELPPVALGLLETLISVDPSQRGTAAFALRSEFFTASPLPCDPSSLPKYPPSKEIDMKLREEEARRRGAAGGKNELEKRGTKDSRTNSAYYPNAGQLQVKQCHSNANGRSEIFGPYQEKTVSGFLVAPPKQARVSKETRKDYAEQPDRASFSGPLVPGPGFSKAGKELGHSITVSRNTNLSTLSSLVTSRTGDNKQKSGPLVSESANQASRYSGPIREMEPARKQDRRSHVRTNIDYRSREDGNSSTKEPALYGRGSAGNKIYVSGPLLVSSNNVDQMLKEHDRRIQEHARRARFDKARVGNNHPQAAVDSKLVSV HDAG 270 CDK typeC MGCIPTIISDGRRRSAAPDKRRPRPRRSSSEGEAPPHATAAGSEGGESARGAPG 82 1749KERPEPAPRFVVRSPQGWPPWLVAAVGHAIGEFVPRCADSFRKLAKIGEGTYSNVYKARDLVTGKTVALKKVRFDNLEAESIKFMAREILVLTRLNHPNVIKLEGPVTSRMSSGLYLAFEYMEHDLSGIAARQNGKFTEPQVKCFMRQLLSGLEHCHNHDVLHRDIKCSNLLIDNEGNLKIADFGLATFYDPERKQVMTNRVVTLWYRAPELLLGATSYGIGIDLWSAGCILAELLYGKPIMPGRTEVEQLHKIFKLCGSPSEAYWNKFKLPNANIFKPPQPYARCIAETFKDFPPSALPLLETLLSIDPDERGTATTALNSEFFAAEPHACEPSSLPKYPPSKEMDLKLIKEKTRRDSSKRPSAIHGSRRDGIHDRAGRVIPAPEATAENQATLHRPRAMKKANPMSRSEKFPPAHMDGVVGSSANAWLSGPASNAAPDSRRHRSLNQNPSSSVGKASTGSSTTQETLKVAPELLQVGSSSLHPC HRMLVYGSNLTIRSK271 CDK type C MGCICAKQADRGPASPGSGILTGAGTGTGTRSSKIPSGLFEFEKSGVKEHGGRS151 1560 GELRKLEEKGSLSKRLRLELGFSHRYVEAEQAAAGWPSWLTAVAGDAIQGLVPLKADSFEKLEKIGQGTYSSVFRARELANGRMVALKKVRFDNFQPESIQFMAREISILRRLDHPNIMKLEGIITSRMSNSIYLVFEYMEHDLYGLISSPQVKFSDAQVKCYMKQLLSGIEHCHQHGVIHRDVKSSNILVNNEGILRIGDFGLANILNPKDRQQLTSHVVTLWYRPPELLMGSTSYGVTVDLWSVGCVFAELMFRKPILRGRTEVEQLHKIFKLCGSPPDGYWKMCKVPQATMFRPRHAYECTLRERCKGIATSAMKLMETFLSIEPHKRGTASSALISEYFRTVPYACDPSSLPKYPPNKEIDAKHREEARRKKARSRVREAEVGKRPTRIHRASQEQGFSSNIAPKEKRSYA 272 CDK type CMAVAAPGHLNVNESPSWGSRSVDCFEKLEQIGEGTYGQVYMAKEKKTGEIVALK 82 1644KIRMDNEREGFPITAIREIKILKKLHHENVIKLKEIVTSPGPEKDEQGRPEGNKYKGGIYMVFEYMDHDLTGLADRPGMRFSVPQIKCYMRQLLTGLHYCHINQVLHRDIKGSNLLIDNEGNLKLADFGLARSFSNDHNANLTNRVITLWYRPPELLLGATKYGPAVDMWSVGCIFAELLHGKPIFPGKDEPEQLNKIFELCGAPDEINWPGVSKIPWYNNFKPTRPMKRRLREVFRHFDRHALELLERMLTLDPSQRISAKDALDAEYFWADPLPCDPKSLPKYESSHEFQTKKKRQQQRQHEETAKRQKLQHPPQHPRLPPVQQSGQAHAQMRPGPNQLMHGSQPPVATGPPGHHYGKPRGPSGGAGRYPSSGNPGGGYNHPSRGGQGGSGGYNSGPYPPQGRAPPYGSSGMPGAGPRGGGGNNYGVGPSNYPQGGGGPYGGSGAGRGSNMMGGNRNQQYGWQQ 273 CDK type CMGCICTKGILPAHYRIKDGGLKLSKSSKRSVGSLRRDELAVSANGGGNDAADRL 626 2782ISSPHEVENEVEDRKNVDFNEKLSKSLQRRATMDVASGGHTQAQLKVGKVGGFPLGERGAQVVAGWPSWLTAVAGEAINGWVPRRADSFEKLEKIGQGTYSSVYRARDLETNTIVALKKVRFANMDPESVRFMAREIIIMRKLDHPNVMKLEGLITSRVSGSLYLVFEYMDHDLAGLAATPSIKLTESQIKCYMQQLLRGLEYCHSHGVLHRDIKGSNLLVDNNGNLKIGDFGLATFFRTNQKQPLTSRVVTLWYRPPELLLGSSDYGASVDLWSSGCILAELFAGKPIMPGRTEVEQLHKIFKLCGSPSEEYWKKSKLPHATIFKPQQPYKRCLLETFKDFPSSALGLLDVLLAVEPECRGTASSALQNEFFTSNPLPSDPSSLPKYPSSKEFDARLRDEEARKHKATAGKARGLESIRKGSKESKVVPTSNANADLKASIQKRQEQSNPRSTGEKPGGTTQNNFILSGQSAKPSLNGSTQIGNANEVEALIVPDRELDSPRGGAELRRQRSFMQRRASQLSRFSNSVAVGGDSHLDCSREKGANTQWRDEGFVARCSHPDGGELAGKHDWSHHLLHRPISLFKKGGEHSRRDSIASYSPKKGRIHYSGPLLPSGDNLDEMLKEHERQIQNAVRKARLDKVKTKREY ADHGQTESLLCWANGR274 CDK type D MDPDPSPDPDPPKSWSIHTRREIIARYEILERVGSGAYSDVYRGRRLSDGLAVA 131467 LKEVHDYQSAFREIEALQILRGSPHVVLLHEYFWREDEDAVLVLEFLRSDLAAVIADASRRPRDGGGGGAAALRAGEVKRWMLQVLEGVDACHRNSIVHRDLKPGNLLISEEGVLKIADFGQARILLDDGNVAPDYEPESFEERSSEQADILQQPETMEADTTCPEGQEQGAITREAYLREVDEFKAKNPRHEIDKETSIFDGDTSCLATCTTSDIGEDPFKGSYVYGAEEAGEDAQGCLTSCVGTRWFRAPELLYGSTDYGLEVDLWSLGCIFAELLTLEPLFPGISDIDQLSRIFNVLGNLSEEVWPGCTKLPDYRTISFCKIENPIGLESCLPNCSSDEVSLVRRLLCYDPAARATPMELLQDKYFTEEPLPVPISALQVPQSKNSHDEDSAGGWYDYNDMDSDSDFEDFGPLKFTPTSTGFSIQFP 275 CDK type DMDPDPSPSPDPPKSWSIHTRREIIARYEILERVGSGAYSDVYRGRRLSDGLAVA 113 1558LKEVHDYQSAFREIEALQILRGSPHVVLLHEYFWREDEDAVLVLEFLRSDLAAVIADASRRPRGGGVAPLRAGEGKRWMLQVLEGVDACHRNSIVHRDLKPGNLLISEEGVLKIADFGQARILLDDGNVAPDYEPESFEERSSEQADILQQPETMEADTTCPEGQEQGAITREAYLREVDEFKAKNPRHEIDKETSIYDGDTSCLATCTTSDIGEDPFKGSYVYGAEEAGEDAQGSLTSCVGTRWFRAPELLYGSTDYGLEVDLWSLGCIFAELLTLEPLFPGISDIDQLSRIFNVLGNLSEEVWPGCTKLPDYRTISFCKIENPIGLESCLPNCSSDEVSLVRRLLCYDPAARATPMELLQDKYFTEEPLPVPISALQVPQSKNSHDEDSAGGWYDYNDMDSDSDFEDFGPLKFTPTSTGFSIQFP 276 Cyclin AMSNQHRRSSFSSSTTSSLAKRHASSSSSSLENAGKAFAAAAVPSHLAKKRAPLG 187 1686NLTNLKAGDGNSRSSSAPSTLVANATKLAKTRKGSSTSSSIMGLSGSALPRYASTKPSGVLPSVNPSIPRIEIAVDPMSCSMVVSPSRSDMQSVSLDESMSTCESFKSPDVEYIDNEDVSAVDSIDRKTFSNLYISDAAAKTAVNICERDVLMEMETDEKIVNVDDNYSDPQLCATIACDIYQHLRASEAKKRPSTDFMDRVQKDITASMRAILIDWLVEVAEEYRLVPDTLYLTVNYIDRYLSGNVMNRQRLQLLGVACMMIAAKYEEICAPQVEEFCYITDNTYFKEEVLQMESSVLNYLKFEMTAPTVKCFLRRFVRAAQGVNEVPSLQLECMANYIAELSLLEYDMLCYAPSLVAASAIFLAKFVITPSKRPWDPTLQHYTLYQPSDLGNCVKDLHRLCFNNHGSTLPAIREKYSQHKYKYVAKKYCP PSIPPEFFHNLVY 277Cyclin A MNKENAVGTKSEAPTIRITRSRSKALGTSTGMLPSSRPSFKQEQKRTVRANAKR 238 1653SASDENKGTMVGNASKQHKKRTVLNDVTNIFCENSYSNCLNAAKAQTSRQGRKWSMKKDRDVHQSGAVQIMQEDVQAQFVEESSKIKVAESMEITIPDKWAKRENSEHSISMKDTVAESSRKPQEFICGEKSAALVQPSIVDIDSKLEDPQACTPYALDIYNYKRSTELERRPSTIYMETLQKDVTPNMRGILVDWLVEVSEEYKLVPDTLYLTVNLIDRSLSQKFIEKQRLQLLGVTCMLIASKYEEICPPRVEEFCFITDNTYTSLEVLKMESRVLNLLHFQLSVPTVKTFLRRFVQAAQVSSEVPSVELEYLANYLAELTLVEYSFLKELPSLMAASAVLLARWTLNQSDNPWNLTLEHYTKYKASELKAAVLALEDLQLNTSGSTLNAIREKYRQQKVNYSLLIHSKANHEIL 278 Cyclin BMAGSDENNPGVVGGAHVQEGLRVGAGKMGAGNVQQRRALSNINSNIIGAPPYPC 235 1539AVNKRVLSEKNVNSENDLLNAAHRPITRQFAAQMAYKQQLRPEENKRTTQSVSNPSKSEDCAILDVDDDKMADDFPVPMFVQHTEAMLEEIDRMEEVEMEDVAEEPVTDIDSGDKENQLAVVEYIDDLYMFYQKAEASSCVPPNYMDRQQDINERMRGILIDWLIEVHYKFELMDETLYLTVNLIDRFLAVQPVVKKKLQLVGVTAMLLACKYEEVSVPVVEDLILISDRAYSRKEVLEMERLMVNTLHFNMSVPTPYVFMRRFLKAAQSDKKLELLSFFIIELSLVEYDMLKFPPSLLAASAIYTALSTITRTKQWSTTCEWHTSYSEEQLLECARLMVTFHQRAGSGKLTGVHRKYSTSKFGHAARTEPANFLLDF RL 279 Cyclin BMASRPIVPVQARGEAAIGGGAGKAAIGGGAGKQQKKNGAAEGRNRKALGDIGNL 158 1618VTVRGIEGKVQPHRPITRSFCAQLLANAQAAAAAENNKKQAVVNVNGAPSILDVPGAGKRAEPAAAAAAAVAKAAQKKVVKPKQKAEVIDLTSDSERAIEAKKKQQHHEPTKKEGEKSSRRNMPTLTSVLTARSKAACGMTKKPKEKVVDIDAGDAHNELAAFEYIEDIYTYYKEAENESLPRNYMSSQPEINEKMRAILVDWLIEIHNKFDLMPETLYLTINIIDRFLSVKAVPRRELQLLGMGALFTASKYEEIWAPEVNDLVCIADRAYSHEQVLAMEKTILGKLEWTLTVPTHYVFLVRFIKASLGDRKLENMVYFLAELGVMNYATLTYCPSMVAASAVYAARCTLGLTPLWNDTLKLHTGFSESQLMDCARLLVGYHAKAKENKLQVVYKKYSSSQREGVALIPPAKALLCEGGGLSSSSSLASSS 280 Cyclin BMGLPDENNAALSKPTNLQVGGLEIGGRKFGQEIRQTRRALSVINQNLVGDRAYP 205 1530CHVVNKRGHSKRDAVCGKDQVDPVHRPLTRKFAAQTASTQQHCIEEAKKPRTAVQERNEFGDCIFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMEDIVEEEEEEPIMDIDGRDKKNPLAVVDYIEDIYANYRRTENCSCVSANYMAQQADINEKMRSILIDWLIEVHDKFDLMHETLFLTVNLIDRFLARQSVVRKKLQLVGLVAMLLACKYEEVSVPVVGDLILISDKAYTRKEVLEMESLMLNSLQFNMSVPTPYVFMRRFLKAAESDKKLEVLSFFLIELSLVEYEMVKFPPSLLAAAAIFTAQCTLYGFKQWTKTCEWHSNYTEDQLLECARMMVGFHQKAATGKLTGVHRKYGTSKFGYTSKCEPAN FLLGEMKNP 281Cyclin B MGLPDENNAALSKPTNLQVGGLEIGGRKFGQEIRQTRRALSVINQNLVGDRAYP 174 1499CHVVNKRGHSKRDAVCGKDQVDPVHRPLTRKFAAQTASTQQHCIEEAKKPRTAVQERNEFGDCIFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMEDIVEEEEEEPIMDIDGRDKKNPLAVVDYIEDIYANYRRTENCSCVSANYMAQQADINEKMRSILIDWLIEVHDKFDLMHETLFLTVNLIDRFLARQSVVRKKLQLVGLVAMLLACKYEEVSVPVVGDLILISDKAYTRKEVLEMEKLMLNSLQFNMSVPTPYVFMRRFLKAAESDKKLEVLSFFLIELSLVEYEMVKFPPSLLAAAAIFTAQCTLYGFKQWTKTCEWHSNYTEDQLLECARMMVGFHQKAATGKLTGVHRKYGTSKFGYTSKCEAAN FLLGEMKNP 282Cyclin D MAMVQRQGHDPSSPQEQEDGPSSFLSDDALYCEEGRFEEDDGGGGGQVDGIPLF 94 1332PSQPADRQQDSPWADEDGEEKEEEEAELQSLFSKERGARPELAKDDGGAVAARREAVEWMLMVRGVYGFSALTAVLAVDYLDRFLAGFRLQRDNRPWMTQLVAVACLALAAKVEETDVPLLVELQEVGDARYVFEAKTVQRMELLVLSTLGWEMHPVTPLSFVHHVARRLGASPHHGEFTHWAFLRRCERLLVAAVSDARSLKHLPSVLAAAAMLRVIEEVEPFRSSEYKAQLLSALHMSQEMVEDCCRFILGIAETAGDAVTSSLDSFLKRKRRCGHLSPRSPSGVIDASFSCDDESNDSWATDPPSDPDDNDDLNPLPKKSRSSSPSSSPSSVPDKVLDLPFMNRIFEGIVNGSPI 283 Cyclin DMEASYQPHHHGHLRQHDPSSSQQEEQVPFDALYCSEEHWGEEDEEEGLASDGLL 176 1342SEERDHRLLSPRALLDQDLLWEDEELASLFSKEEPGGMRLNLENDPSLADARREAVEWIMRVHAHYAFSALTALLAVNYWDRFTCSFALQEDKPWMTQLSAVACLSLAAKVEETQVPLLIDFQVEDSSPVFEAKNIQRMELLVLSSLEWKMNPVTPLSFLDYMTRRLGLTGHLCWEFLRRCENVLLSVISDCRFTCYLPSVIAASTMLHVINGLKPRLDVEDQTQLLGILAMGMDKIDACYKLIDDDHALRSQRYSHNKRKFGSVPGSPRGVMELCFSSDGSNDSWSVAASVSSSPEPHSKKSRAGEEAEDRLLRGLEGEEDDP ASADIFSFPH 284Cyclin D MALQEEDTRRHYPTAPPFSPDGLYCEDETFGEDLADNACEYAGGGARDGLCEIK 150 1283DPTLPPSLLGQDLFWEDGELASLVSRETGTHPCWDELISDGSVALARKDAVGWILRVHGHYGFRPLTAMLAVNYLDRFFLSRSYQRDRPWISQLVAVACLSVAAKVEETQVPILLDLQVANAKFVFESRTIQRMELLLMSTLDWRMNSVTPISFFDHILRRFGLTTNLHRQFFWMCERLLLSVVADVRLASFLPSVVATAAMLYVNKEIEPCICSEFLDQLLSLLKINEDRVNECYELILELSIDHPEILNYKHKRKRGSVPSSPSGVIDTSFSCDSSNDSWGVASSVSSSLEPRFKRSRFQDQQMGLPSVNVSSMGVLNSSY 285 Cyclin-MGQIQYSEKYFDDTYEYRHVVLPPDVAKLLPKNRLLSENEWRAIGVQQSRGWVH 101 367 dependentYAIHRPEPHIMLFRRPLNYQQQQENQAQQNMLAK kinase regulatory subunit 286 HistoneMGSIDPPKAEQNGTAAAAVADPGQKPGAGDAMPPPPPVKHSNGTAAEPDVATKR 9 1352acetyltransferase RRMSVLPLEVGTRVMCRWRDGKYHPVKVIERRKLNPGDPNDYEYYVHYTEFNRRLDEWVKLEQLDLNSVETVVDEKVEDKVTGLKMTRHQKRKIDETHVEGHEELDAASLREHEEFTKVKNIATIELGRYEIETWYFSPFPPEYNDCSKLYFCEFCLNFMKRKEQLQRHMKKCDLKHPPGDEIYRSGTLSMFEVDGKKNKVYGQNLCYLAKLFLDHKTLYYDVDLFLFYVLCECDDRGCHMVGYFSKEKHSEESYNLACILTLPPYQRKGYGKFLIAFSYELSKKEGKVGTPERPLSDLGLLSYKGYWTRVLLDILKKHKANISIKELSDMTAIKADDILNTLQSLDLIQYRKGQHVICADPKVLDRHLKAAGRGGLE VDVSKLIWTPYREQG287 Histone MAQKHSTAPDPAAEPKKRRRVGFSGIDAGVDPNGCFKVYLVSREEEVGAPDSFC 891486 acetyltransferaseLDPVDLSHFFEEEDGKIYGYEGLKISVWVSCVSFHSYAEIAFESKSDGGKGITDLNTALKNMFGETLVDNKDDFLQTFSKETQFIRSTVSAGEILKHKHSDDHVNDSVSNLKVGSDVEAVRMLMGDMTAGHLYSRLVPLVLLLVDGSSPIDVTDSSWELYLLIQKTSDQQGNFHDRLLGFAAVYRFYHYPDSSRLRLGQILVLPLYQRKGYGRYLLEVLNNVAIADDVYDFTIEEPVDNLQHLRTCIDVQRLLSFDKVQQAVNSTVSQLKQGKLSKKTYIPRLLPPPSVVEDARKRFKINKKQFLQCWEILVYLGLDPADKSIQDYFSVISNRVRADILGKDSETAGKKVIEVPSDFDPEMSFVMHRAKAGGEANGIQVEDNQNKQEEQLQQLIDERLKDIKLIAEKVTQK 288 HistoneMAQKHSTAPDPAAEPKKRRRVGFSGIDAGVDPNGCFKVYLVSREEEVGAPDSFC 89 1477acetyltransferase LDPVDLSHFFEEEDGKIYGYEGLKISVWVSCVSFHSYAEIAFESKSDGGKGITDLNTALKNMFGETLVDNKDDFLQTFSKETQFIRSTVSAGEILKHKHSDGHVNDSVSNLKVGSDVEAVRMLMGDMTAGHLYSRLVPLVLLLVDGSNPIDVTDSSWELYLLIQKTSDQQGNFHDRLLGFAAVYRFYHYPDSLRLRLGQILVLPLYQRKGYGHYLLEVLNNVAIADDVYDFTIEEPVDNLQHLRTCIDVQRLLSFDKVQQAVNSTVSQLKQGKLSKKTYIPRLLPPPSVVEDARKRFKINKKQFLQCWEILVYLGLDPADKSIQDYFSVISNRVRADILGKDSETAGKKVIEVPSDFDPEMSFVLHRAKAGGETNGIQVEDNQNKQEEQLQQLIDERLKDIKLIAQKVSRK 289 HistoneMALPMEFWGVEVKAGQPLKVNPGNAKILHLSQASLGECKSSKGNESVPLHVKFG 160 1062deacetylase DQKLVLGTLSTENFPQLAFDLVFEKEFELSHNWKSGSVYFCGYKSVVHDDDDEFSDLESDSEEEDLPMIGVENGKVAAQASAKTATASANASKVESSGKQKARIPQPMKVDEDDSDEDDDDEDEDESDEEGVDGEADSDEEEDESDEEETPKKAEIGKKRAADSATKTPVPAKKSKLPTPQKTDGKKGGHTATPHPAKQAGKNPANSANKSQSPKSAGQVSCKSCSKTFNSDGALQSHSKAKHGGK; 290 HistoneMEFWGVEVKAGQPLKVNPGNAKILHLSQASLGECKSSKGNESVPLHVKFGDQKL 172 1077deacetylase VLGTLSTENFPQLAFDLVFEKEFELSHNWKSGSVYFCGYKSVVHDDDDEFSDLESDSEEEDLPMIGVENGKVAAQASAKTATASANASKVESSGKQKASIPQPMKVDEDDSDEDDDEDDDDEDESDEGVDGEADSDEEEDESDEEETPKKAEIGKKRAADSATKTPVPAKKSKLPTPQKTDGKKGGHTATPHPAKQAGKNPANSANKSQSPKSAGQVSCKSCSKTFNSDGALQSHSKAKHGGK 291 HistoneMEFWGVEVKSGEPLNVEPGAETVVHLSQACLGETKEKTKESVLLYVHIGVQKLV 66 989deacetylase LGTLSADKFPQIPFDLVFEKSFKLSHNWKNGSVFFSGYKTLLPCGSDADSPYSDSDTDEGLPINVTAQADVPAKKAPVTANANAAKPNLASAKQKVKIVESNEDGKNEGDDDEDADVSSDDDAEDDSGDEDMVDGGDESSDEDDDDSEEGESSEEEEPKAQPSKKRPADSVLKTPASDKKSKLETPQKTDGKKASEHVATPYPSKQAGKAIASKGQAKQQTPNSNEFSCKPCNRSFKSDQALQSHNKAKHGGS 292 HistoneMDTGGNSLPSGPDGVKRKVCYFYDPEVGNYYLLQHMQVLKPVPARDRDLCRFHA 111 1541deacetylase DDYVAFLRSITPETQQDQLRQLKRFNVGEDCPVFDGLHSFCQTYAGGSVGGAVKLNHGLCDIAINWAGGLHHAKKCEASGFCYVNDIVLGILELLKQHERVLYVDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGDIRDIGYGKGKYYSLNVPLDDGIDDESYHSLFKPIIGKVMEVFKPGAVVLQCGADSLSGDRLGCFNLSIKGHAECVRYMRSFNVPVLLLGGGGYTIRNVARCWCYETGVALGLEVDDKMPQHEYYEYFGPDYTLHVAPSNMENKNSRQLLEEIRSKLLENLSKLQHAPSVPFQERPPDTELPEADEDQEDPDERWDPDSDMDVDEDRKPLPSRVKRELIVEPEVKDQDSQKASIDHGRGLDTTQEDNASIKVSDMNSMITDEQSVKMEQDNVNKPSEQIFPK 293 HistoneMDTGGNSLPSGPDGVKRKVCYFYDPEVGNYYYGQGHPMKPHRIRMTHALLAHYG 116 1615deacetylase LLQHMQVLKPVPARDRDLCRFHADDYVAFLRSITPETQQDQLRQLKRFNVGEDCPVFDGLHSFCQTYAGGSVGGAVKLNHGLCDIAINWAGGLHHAKKCEASGFCYVNDIVLGILELLKQHERVLYVDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGDIRDIGYGKGKYYSLNVPLDDGIDDESYHSLFKPIIGKVMEVFKPGAVVLQCGADSLSGDRLGCFNLSIKGHAECVRYMRSFNVPVLLLGGGGYTIRNVARCWCYETGVALGLEVDDKMPQHEYYEYFGPDYTLHVAPSNMENKNSRQLLEDIRSKLLENLSKLQHAPSVPFQERPPDTELPEADEDQEDPDERWDPDSDMDVDEDRKPLPSRVKRELIVEPEVKDQDSQKASIDHGRGLDTTQEDNASIKVSDMNSMITDEQSVKMEQ DNVNKPSEQIFPK 294Histone MRPKDRISYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVLSYELHTKMEIYRPHK 155 1453deacetylase AYPAELAQFHSPDYVEFLHRITPDTQHLFPNDLAKYNLGEDCPVFENLFEFCQIYAGGTIDAARRLNNQLCDIAINWAGGLHHAKKCEASGFCYINDLVLGILELLKYHARVLYIDIDVHHGDGVEEAFYFTDRVMTVSFHKFGDMFFPGTGDVKEIGGKEGKFYAINVPLKDGIDDTSFTRLFKAIISKVVETYQPGAIVLQCGADSLAGDRLGCFNLSIDGHSECVRFVKKFNLPLLVTGGGGYTKENVARCWVVETGVLLDTELPNEIPENEYFKYFAPDYSLKIPRGNIVLENLNSKSYLSAIKVQVLENLENIQHAPSVQMQEVPPDFYIPDFDEDEQNPDERMDQHTQDKQIQRDDEYYDGDNDNDHNMDDS 295 HistoneMTVAEDFHVNNRSKMVSQATPESRLTGGEDDNSLHNQVDELLCQELPERQVILE 228 2033deacetylase FEGTRPKPYFSDHNGGENSALGVRATEDDLNSDVEAEEKQKEMITLEDMYKNDGTLYDDDEDDSDWEPVKRQVELMRWFCTNCTMVNVEDVFLCDICGEHRDSGILRHGFYASPFMQDVGAPSVEAEVQESREDHARSSPPSSSTVVGFDEKMLLHSEVEMKSHPHPERADRLQAIAASLATAGIFPGRCRSLPVREITKEELQMVHSSEHVDAVEMTSHMFSSYFTPDTYANEHSARAARIAAGLCADLASTIISGRSKNGFALVRPPGHHAGIKHAMGFCLHNNAAVAALAAQGAGAKKVLIVDWDVHHGNGTQEIFDGNKSVLYISLHRHEGGNFYPGTGAAHEVGTMGAEGYCVNIPWSRRGVGDNDYVFAFHHIVLPIASAFAPDFTIISAGFDAARGDPLGCCDVTPAGYAQMTHMLSALSGGKLLVILEGGYNLRSISSSAVAVIKVLLGDSPISEIADAVPSKAGLRTVLEVLKIQRSYWPSLESIFWELQSQWGIFLVDNRRKQIRKRRRVLVPIWWKWGRKSVLYHLLNGH LHVKTKR 296Histone MAAAPSSPPTNRVDVFWHDGMLSHDTGRGVFDTGSDPGFLDVLEKHPENPDRVR 110 1258deacetylase NMVSILKRGPISPFISWHTATPALISQLLSFHSPEYINELVEADKNGGKVLCAGTFLNPGSWDAALLAAGNTLSAMKYVLDGKGKIAYALVRPPGHHAQPSQADGYCFLNNAGLAVRLALDSGCKRVVVVDIDVHYGNGTAEGFYQSSDVLTISLHMNHGSWGPSHPQSGSVDELGEDEGYGYNMNIPLPNGTGDRGYEYAVTELVVPAVESFKPEMVVLVVGQDSSAFDPNGRQCLTMDGYRAIGRTIRGLADRHSGGRILIVQEGGYHVTYSAYCLHATVEGILDLPDPLLADPIAYYPEDEAFPVKVVDSIKRYLVDKVPF LKEH 297 HistoneMVESSGGASLPSVGQDARKRRVSYFYEPTIGDYYYGQGHPMKPHRIRMAHNLIV 50 1462deacetylase HYYLHRRMEISRPFPAATTDIRRFHSEDYVTFISSVTPETVSDPAFSRQLKRFNVGEDCPVFDGIFGFCQASAGGSMGAAVKLNRGDSDIALNWAGGLHHAKKSEASGFCYVNDIVLGILELLKVHKRVLYVDIDVHHGDGVEEAFYTTDRVMTVSFHKFGDFFPGSGHIKDTGAGPGKNYALNVPLNDGIDDESFRGMFRPIIQKVMEVYQPDAVVLQCGADSLSGDRLGCFNLSVKGHADCLRFLRSFNVPLMVLGGGGYTMRNVARCWCYETAVAVGVEPENDLPYNEYYEYFGPDYTLHVEPCSMENLNAPKDLERIRNMLLEQLSRIPHAPSVPFQMTPPITQEPEEAEEDMDERPKPRIWNGEDYESDAEEDKSQHRSSNADALHDENVEMRDSVGENSGDKTREDRSPS 298 MAT1 CDK-MVVPSSNPHNREMAIRRRMASTFNKREDDFPSLREYNDYLEEVEEMTFNLIEGV 176 739activating DVPTIEAKIAKYQEENAEQIMINRAKKAEEFAAALAASKGLPPQTDPDGALNSQ kinaseassembly AGLSVGTQGQYAPAIAGGQPRPTGMAPQPVPLGTGLDTHGYDDEEMIKLRAERG factorGRAGGWSIELSKKRALEEAFGSLWL 299 PeptidylprolylMAAIISCHHYHSCCSSLIASKWVGARIPTSCFGRSSTQSNNAASVRQFVTRCSS 150 1529isomerase SPSSRGQWQPHQNGEKGRSFSLRECAISIALAVGLVTGVPSLDMSTGNAYAASPALPDLSVLISGPPIKDPEALLRYALPINNKAIREVQKPLEDITDSLKVAGLRALDSVERNVRQASRVLKQGKNLIVSGLAESKKDHGVELLDKLEAGMDELQQIVEDGNRDAVAGKQRELLNYVGGVEEDMVDGFPYEVPEEYKNMPLLKGRAAVDMKVKVKDNPNLEECVFRIVLDGYNAPVTAGNFVDLVERHFYDGMEIQRADGFVVQTGDPEGPAESFIDPSTEKPRTIPLEIMVDGEKAPVYGATLEELGLYKAQTKLPFNAFGTMAMARDEFEDNSASSQIFWLLKESELTPSNANILDGRYAVFGYVTENQDFLADLKVGDVIESVQVVSGLDNLANPSYKIAG; 300 PeptidylprolylMAGEDFDIPPADEMNEDFDLPDDDDDAPVMKAGDEKEIGKQGLKKKLVKEGDAW 247 1971isomerase ETPDNGDEVEVHYTGTLLDGTQFDSSRDRGTPFKFTLGQGQVIKGWDQGIKTMKKGENAIFTIPPELAYGEAGSPPTIPPNATLQFDVELLSWTSVKDICKDGGIFKKILVEGEKWENPKDLDEVLVKYEFQLEDGTTIARSDGVEFTVKEGHFCPAVAKAVKTMKKGEKVLLTVKPQYGFGEKGKPASGDEGAVPPNATLQITLELVSWKTVSEVTDDKKVIKKILKEGEGYERPNEGAVVEVKLIGKLQDGTVFVKKGHDDCEELFKFKIDEEQVVDGLDKAVMNMKKGEVALLTVAPEYAFGSSESKQDLAVVPPSSTVYYEVELVSFVKDKESWDMNTEEKIEAAGKKKEEGNVIFKAGKYAKASKRYEKAVKYIEYDTSFSEDEKKQAKALKVACNLNDAACKLKLKDYNQAEKLCTKVLELDSRNVKALYRRAQAYIELSDLDLAEFDIKKALEIDPHNRDVKLEYKVLKEKVKEFNKKDAKFYGNMFAKMSKLEPVEKTAAKEPEPMSIDSKA; 301 PeptidylprolylMSTVYVLEPPTKGKVVLNTTHGPLDVELWPKEAPKAVRNFVQLCLEGYYDNTIF 136 1644isomerase HRIIKDFLVQGGDPTGSGTGGESIYGDAFSDEFHSRLRFKHRGLVACANAGSPHSNGSQFFITLDRCDWLDRKNTIFGKITGDSIYNLSGLAEVETDKSDRPLDPPPKIISVEVLWNPFEDIVPRAPVRSLVPTVPDVQNKEPKKKAVKKLNLLSFGEEAEEEEKALVVVKQKIKSSHDVLDDPRLLKEHIPSKQVDSYDSKTARDVQSVREALSSKKQELQKESGAEFSNSFREIADDEDDDDDDASFDARMRRQILQKRKELGDLPPKPKPKSRDGISARKERETSISRDKDDDDDDDQPRVEKLSLKKKGIGSEARGERMANADADLQLLNDAERGRQLQKQKKHRLRGREDEVLTKLETFKASVFGKPLASSAKVGDGDGDLSDWRSVKLKFAPEPGKDRMTRNEDPNDYVVVDPLLEKGKEKFNRMQ AKEKRRGREWAGKSLT;302 PeptidylprolylMASAISMHSSGLLLLQGTNGKDVTEMGKAPASSRVANMQQRKYGATCCVARGLT 48 836 isomeraseSRSHYASSLAFKQFSKTPSIKYDRMVEIKAMATDLGLQAKVTNKCFFDVEIGGEPAGRIVIGLFGDDVPKTVENFRALCTGEKGFGYKGCSFHRIIKDFMIQGGDFTRGNGTGGKSIYGSTFEDENFALKHVGPGVLSMANAGPSTNGSQFFICTVKTPWLDNRHVVFGQVVDGMDVVQKLESQETSRSDVPRQPCRIVNCGELPLDG; 303 PeptidylprolylMAASFTALSNVGSLSSPRNGSEIRRFRPSCNVAASVRPPPLKAGLSASSSSSFS 49 822 isomeraseGSLRLIPLSSSPQRKSRPCSVRASAEAAAAQSKVTNKVYLDISIGNPVGKLVGRIVIGLYGDDVPQTAENFRALCTGEKGFGYKGSTVHRVIKDFMIQGGDFDKGNGTGGKSIYGRTFKDENFKLSHVGPGVVSMANAGPNTNGSQFFICTVKTPWLDQRHVVFGQVLEGMDIVRLIESQETDRGDRPRKRVVVSDCGELPVV; 304 PeptidylprolylMAEAIDLTGDGGVMKTIVRRAKPDAVSPSETLPLVDVRYEGVLAETGEVFDSTH 185 751 isomeraseEDNTLFSFEIGKGSVISAWDTALRTMKVGEVAKITCKPEYAYGSTGSPPDIPPDATLIFEVELVACKPCKGFSVTSVTEDKARLEELKKQREIAAATKEEEKKRREEAKAAAAARVQAKLDAKKGHGKGKGKAK; 305 PeptidylprolylMGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRALCTGEKGAGRSGKPLH 103 621 isomeraseYKGSSFHRVIPGFMCQGGDFTAGNGTGGESIYGSKFADENFVKKHTGPGVLSMANAGPGTNGSQFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSSGRTSKP VVVADCGQLS 306Peptidylprolyl MPNPKVFFDMTIGGAAAGRVVMELYADTTPRTAENFRALCTGEKGVGRSKKPLH 41559 isomerase YKGSKFHRVIPSFMCQGGDFTAGNGTGGESIYGVKFADENFIKKHTGPGILSMANAGPGTNGSQFFICTTKTEWLDGKHVVFGKVVEGMEVVKAIEKVGSSSGRTSKP VVVADCGQLP 307Peptidylprolyl MAEAIDLTGDGGVMKTIVRRAKPDAVSPSETLPLVDVRYEGVLAETGEVFDSTH127 693 isomerase EDNTLFSFEIGKGSVISAWDTALRTMKVGEVAKITCKPEYAYGSTGSPPDIPPDATLIFEVELVACKPCKGFSVTSVTEDKARLEELKKQREIAAATKEEEKKRREEAKAAAAARVQAKLDAKKGHGKGKGKAK 308 PeptidylprolylMATARSFFLCALLLLATLYLAQAKKSEDLKEVTHKVYFDVEIAGKPAGRIVMGL 28 639 isomeraseYGKAVPKTAENFRALCTGEKGTGKSGKPLHYKGSSFHRIIPSFMLQGGDFTLGDGRGGESIYGEKFADENFKLKHTGPGLLSMANAGPDTNGSQFFITTVTTSWLDGRHVVFGKVLSGMDVVYKVEAEGRQSGTPKSKVVIADSGELPL 309 PeptidylprolylMMRREISVLLQPRFVLAFLALAVLLLVFAFPFSRQRGDQVEEEPEITHRVYLDV 135 812 isomeraseDIDGQHLGRIVIGLYGEVVPRTVENFRALCTGEKGKSANGKKLHYKGTPFHRIISGFMIQGGDVIYGDGKGYESIYGGTFADENFRIKHSHAGIISMVNSGPDSNGSQFFITTVKASWLDGEHVVFGRVIQGMDTVYAIEGGAGTYNGKPRKKVIIADSGEI PKSKWDEER 310Peptidylprolyl MWATAEGGPPEVTLETSMGSFTVELYFKHAPRTSRNFIELSRRGYYDNVKFHRI119 613 isomerase IKDFIVQGGDPTGTGRGGESIYGKKFEDEIKPELKHTGAGILSMANAGPNTNGSQFFITLAPCPSLDGKHTIFGRVCRGMEIIKRLGSVQTDNNDRPIHDVKILRTSV KD 311Peptidylprolyl MSNPKVFFDILIGKMKAGRVVMELFADVTPKTAENFRALCTGEKGIGRSGKPLH 38562 isomerase YKGSTFHRIIPNFMCQGGDFTRGNGTGGESIYGMKFADENFKIKHTGLGVLSMANAGPDTNGSQFFICTEKTPWLDGKHVVFGKVIDGYNVVKEMESVGSDSGSTRET VAIEDCGQLSEN 312Peptidylprolyl MDDDFEFPASSNVENDDDDGMDMDDMGGDVPEEEDPVASPAVLKVGEEREIGKA109 1872 isomeraseGFKKKLVKEGEGWETPSSGDEVEVHYTGTLLDGTKFDSSRDRGTPFKFKLGRGQVIKGWDEGIKTMKKGENAIFTIPPELAYGESGSPPTIPPNATLQFDVELLSWSSVKDICKDGGILKKVLVEGEKWDNPKDLDEVFVKYEASLEDGTLISKSDGVEFTVGDGYFCAALAKAVKTMKKGEKVLLTVMPQYAFGETGRPASGDEAAVPPDASLQIMLELVSWKTVSDVTKDKKVLKKTLKEGEGYERPNDGAAVQVRLCGKLQDGTVFVKKDDEEPFEFKIDEEQVIDGLDRAVKNMKKGEVALVTIQPEYAFGPTESQQDLAVVPANSTVYYEVELLSFVKEKESWEMNNQEKIEAAARKKEEGNAAFKAGKYVRASKRYEKAVRFIEYDSSFSDEEKQQAKTLKNTCNLNDAACKLKLKDFKEAEKLCTKVLEGDGKNVKALYRRAQAYIQLVDLDLAEQDIKKALEIDPNNRDVKLEYKILKEKVREYNKRDAQFYGNMFAKMNKLEHSRTAGMGAKHEAAPMTIDSKA 313 PeptidylprolylMAKPRCFMDISIGGELEGRIVGELYTDVAPKTAENFRALCTGEKGIGPHTGAPL 74 1159 isomeraseHYKGVRFHRVIKGFMVQGGDISAGDGTGGESIYGLKFEDENFDLKHERKGMLSMANSGPNTNGSQFFITTTRTSHLDGKHVVFGRVVKGMGVVRSVEHVTTAAGDCPTVDVVIADCGEIPAGADDGIRNFFKDGDTYPDWPADLDESPAELSWWMDAVDSIKAFGNGSYKKQDYKMALRKYRKALRYLDICWEKEGIDEVESSSLRKTKSQIFTNSSACKLKLCDLKGALLDAEFAVRDGENNAKAYFRQGQAHMELNDIDAAAESFSKALELEPNDVGIKKELNAAKKKIFERREQEKRAYRKMFL 314 PeptidylprolylMTKRKNPLVFLDVSIDGDPVERIVIELFADTVPRTAENFRSLCTGEKGVGKTTG 54 2045 isomeraseKPLHYKGSYFHRIIKGFMAQGGDFSNGNGTGGESIYGGKFADENFKLAHDGPGLLSMANGGPNTNGSQFFIIFKRQPHLDGKHVVFGKVMRGMEVVKKIEQVGSANGKPLQPVKIVDCGETSETGTQDAVVEEKSKSATLKAKKKRSARDSSSESRGKRRQRKSRKERTRKRRRYSSSDSYSSESSDSDSESYSSDTESESKSHSESSVSDSSSSDGRRRKRKSTKREKLRRQRGKDSRGEQKSARYDKKSRHKSADSSSDSESESSSRSRSRDDKKKSSRRESARSVSKLKDAEANSPENLESPRDREIKKVEDNSSHEEGEFSPKNDVQHNGHGTDAKFGKYDDQRPRSDGSKKSSGSMRDSPKRLANSVPQGSPSSSPAHKASEPSSSIRARNPSRSPAPDGNSKRIRKGRGFTERFSYARRYRTPSPEDVTYRPYHYGRRNFHDRRNDRYSNYRSYSERSPHRRYRSPPRGRSPPRYQRRRSRSRSVSRSPGGNKGRYRGRDQSRSRSRSRSRSPRRGSSPANKQLPLSERLKSRLGTRVDEHSPRRRRSSSRSHDSSRSRSPDEVPDKHEGKAAPVSPARSRSSSPSGR GLVSYGDASPDSGIN315 PeptidylprolylMSVLLVTSLGDIVVDLHADRCPLTCKNFLKLCRIKYYNGCVFHTVQKDFTAQTG 53 1879 isomeraseDPTGTGTGGDSVYKFLYGDQARFFMDEIHLDLKHSKTGTVAMASGGENLNASQFYFTLRDDLDYLDGKHTVFGEVAEGLETLTRINEAYVDEKGRPYKNIRIRHTYILDDPFDDPPQLAELIPDASPEGKPKDEVVDDVRLEDDWVPLDEQLGPAQLEEAIRAKEAHSRAVVLESIGDIPDAEIKPPDNVLFVCKLNPVTEDEDLHTIFSRFGTVVSADVIRDFKTGDSLCYAFIEFENKDSCEQAYFKMDNALIDDRRIKVDFSQSVAKLWSQFKRKDSQAAKGKGCFKCGAPDHMARECPGSSTRQPLSKYILKEDNAQRGGDDSRYEMVFDEDAPESPSHGKKRRGRDDRDDRHKMSRQSVEETKFNDREGGHSVDKHRQSERSKHREDEMSRDSKASEAGRRRIDRDFPEEERDGEKYTESHRDRDGKRGDYRDYRKGEADVQTHGDRRGDENYRRKSAAYDDGHEGAGAARRKDSNDDHHAYRRGYGDSRKGTRDEDDDGRGRRDDPSYRRSSGHKDSSNGGREEQKYRSGETDG KSHPERSHRGDRRR316 PeptidylprolylMRPFNGGSSIACLVLVIAAGALAESQGPHLGSARVVFQTNYGDIEFGFFPGVAP 7 690 isomeraseRTVDHIFKLVRLGCYNTNHFFRVDKGFVAQVADVANGRTAPMNDEQRTEAEKTIVGEFSNVKHVRGILSMGRYDDPDSAQSSFSILLGDAPHLDGKYAIFGRVTKGDETLKKLEQLPTRREGMFVMPTERITILSSYYYDTGAESCEEENSTLRRRLAASAV EVERQRMKCFP 317Peptidylprolyl MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGTGRSGKPLH 83601 isomerase FKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP VVIADSGQLA 318Peptidylprolyl MRFTSITSAIALFAAAASALDKPLDIKVDKAVECSRKTKAGDKIQVHYRGTLEA125 535 isomerase DGSEFDASYKRGQPLSFHVGKGQVIKGWDQGLLDMCPGEKRTLTIQPDWGYGSRGMGPIPANSVLIFETELVEIAGVAREEL 319 PeptidylprolylMGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRALCTGEKGAGRSGKPLH 55 573 isomeraseYKGSSFHRVIPGFMCQGGDFTAGNGTGGESIYGSKFADENFVKKHTGPGVLSMANAGPGTNGSQFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSSGRTSKP VVVADCGQLS 320Peptidylprolyl MAVATRSRWVAMSVAWILVLFGTLALIQNRLSDTGASSDPKLVHRKVGEEKKKP147 842 isomerase DDLEEVTHKVFFDVEIGGKPAGRIVMGLFGKTVPKTVENFRALCTGEKGIGKSGKPLNYKGSQFHRIIPKFMIQGGDFTLGDGRGGESIYGNKFSDENFKLKHTDAGRLSMTNAGPDTNGSQFFITTVTTSWLDGRHVVFGKVLSGMDVVHKIEAEGGQSGQ PKSIVVISDSGELDL321 PeptidylprolylMAVTLHTNLGDIKCEIFCDEVPKAAEHNARGILSMANSGPNTNGSQFFIAYAKQ 167 487 isomerasePHLNGLYTIFGRVIHGFEVLDIMEKTQTGPGDRPLAEIRLNRVTIHANPLAG 322 PeptidylprolylMAVATRSRWVAMSVAWILVLFGTLALIQNRLSDTGASSDPKLVHRKVGEEKKKP 195 890 isomeraseDDLEEVTHKVFFDVEIGGKPAGRIVMGLFGKTVPKTVENFRALCTGEKGIGKSGKPLNYKGSQFHRIIPKFMIQGGDFTLGDGRGGESIYGNKFSDENFKLKHTDAGRLSMANAGPDTNGSQFFITTVTTSWLDGRHVVFGKVLSGMDVVHKIEAEGGQSGQ PKSIVVISDSGELDL323 PeptidylprolylMGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRALCTGEKGAGRSGKPLH 68 586 isomeraseYKGSSFHRVIPGFMCQGGDFTAGNGTGGESIYGSKFADENFVKKHTGPGVLSMANAGPGTNGSQFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSSGRTSKP VVVADCGQLS 324Retinoblastoma MSPVAANAMEEAAEPEVPAPVTPSKDDADTDAAVSRFLGFCKSKLGLAEGNCVQ182 3265 related proteinSSTLLRKTAHVLRSSGTVIGTGTAEEAERYWFAFVLYTVRRVGERKAEDEQNGSDETEVPLSRILKASVLNLIDFFKEIPQFVIKAGAIVSGIYGANWDSRLEAREMQTNYVHLCILCKFYKRICGEFFILNDAKDDMKSADSSTSDPVIMYQPFGWLLFLALRIHALSRFKDLVSSTNALVSVLAILIIHLPTRFRKFSISDSSQLVKRSEKGVDLVGSLAYRYDTSEDEIKRTLEKANNVIAEILGITPPPASECKAENLENVDTDGLIYFGNLMEETSLSSILSTLEKIYEDATRNDSEFDERVFINDDDSLLVSGSLSGAAINLTGAKRKYDSFASPAKTITRPLSPSRSPASHINGIIGGTNLRITATPVATAMTTAKWLRTFVSPLPSKPSTDLQGFLASCDRDVTSDVIRRANIILEAIFPNSPIGERTVTGGLQNANLMDNMWAEQRRLEALKLYYRVLEAMCRAEAQILHSNNLTSLLTNERFHRCMLACSAELVLATHKTVTMLFPAVLERTGITAFDLSKVIESFVRHEETLPRELRRHLNTLEERLLENMVWERGSSMYNSLVVARPALAPEINRLGLLPEPMPSLDAIALLINFSSSGLPQSPVQKHEASPGQNGDIRSPKRISTEYRSVLVERNFTSPVKDRLLALSNIKSKLPPPPLQSAFASPTRPHPGGGGETCAETAIHIFFSKITKLAAVRINAMLERLQLSQQIKEGVYCLFQQILSQRTNLFFNRHIDQVILCCFYGVAKINQINLTFREIIYNYRKQPQCKPQVFRNVFVDWSTRRNGKAGNEHVDIISFYNEIFIPSVKPLLVELGPTGATTRTNRTSEVGNKNDAQCPGSPKISSFPTLPDMSPKKVSASHNVYVSPLRSSKMDASISHSSKSYYACVGESTHAYQSPSKDLVAINSRLNGNRKVRGTLNFDDVDAGLVSDSMVANSLYLQNGSSMSSSTAKSSEKPES 325 WD40 repeatMRPILMKGHERPLTFLKYNREGDLLFSCAKDHTPTVWFADNGERLGTYRGHNGA 165 1145 proteinVWCCDVSRDSMRLITGSADTTAKLWSVQNGTQLFTFNFDSPARSVDFSIGDKLAVITTDPFMELPSAIHVKRIARDPADQASESVLVLRGHQGRIARAVWGPLNKTIISAGEDAVIRIWDSETGKLLRESDKETGHKKAVTSLMKSVDGSHFVTGSQDKSAKLWDIRTLTLIKTYVTERPVNAVTMSPLLDHVVLGGGQDASAVTMTDHRAGKFEAKFFDKILQEEIGGVKGHFGPINALAFNPDGKSFSSGGEDGYVRLHHFDPDYFNI KI 326 WD40repeat MDKKRTVVPLVCHGHSRPVVDLFYSPITPDGFFLISASKDSSPMLRNGETGDWI 529 1569protein GTFEGHKGAVWSCCLDTNALRAASGSADFSAKLWDALSGDELHSFEHKHIVRSCAFSEDTHLLLTGGVEKILRIFDLNRPDAPPREVDNSPGSIRTVAWLHSDQTILSSCTDIGGVRLWDVRSGKIVQTLETKSPVTSSEVSQDGRYITTADGSTVKFWDANHFGLVKSYNMPCNIESASLEPKLGNKFIAGGEDMWVHIFDFHTGEEIGCNKGHHGPVHCVRFSPGGESYASGSEDGTIRIWQTGPANNVEGDANPSNGPVTGKAKVGADEVTRKVEDLQIGKEGKDWREG 327 WD40 repeatMAEGLILKGTMRAHTDMVTAIAIPIDNSDMVVTSSRDKSIILWHLTKEEKVYGV 156 1136 proteinPRRRLTGHSHFVQDVVLSSDGQFALSGSWDGELRLWDLATGVSARRFVGHTKDVLSVAFSIDNRQIVSASRDRTIKLWNTLGECKYTIQEGEAHTDWVSCVRFSPNTLQPTIVSASWDRTIKVWNLTNCKLRNTLAGHNGYVNTVAVSPDGSLCASGGKDGVILLWDLAEGKRLYNLEAGAIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVEDLRVDLKNEADKTDGTTTAASNKKVIYCTSLNWSADGSTLFSGYNDGVIRVWGTG RY 328 WD40repeat MAEGLHLKGTMKAHTDMVTAIAVPIDNADMIVTSSRDKSIILWHLTKEDKVYGV 90 1073protein PRRRLTGHSHFVQDVVLSSDGQFALSGSWDGELRLWDLATGVSARRFVGHTKDVLSVAFSIDNRQIVSASRDRTIKLWNTLGECKYTIQEGEAHNDWVSCVRFSPNTLQPTIVSASWDRTVKVWNLTNCKLRNTLQGHSGYVNTVAVSPDGSLCASGGKDGVILLWDLAEGKKLYSLEAGAIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVEDLRVDLKNEADMSDGTTGAMSSNKKVIYCTSLNWSADGSTLFSGYNDGVIRVWGI GRY 329 WD40repeat MAEGLHLKGTMKAHTDMVTAIAVPIDNADMIVTSSRDKSIILWHLTKEDKVYGV 66 1049protein PRRRLTGHSHFVQDVVLSSDGQFALSGSWDGELRLWDLATGVSARRFVGHTKDVLSVAFSIDNRQIVSASRDRTIKLWNTLGECKYTIQEGEAHNDWVSCVRFSPNTLQPTIVSASWDRTVKVWNLTNCKLRNTLQGHSGYVNTVAVSPDGSLCASGGKDGVILLWDLAEGKKLYSLEAGAIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVEDLRVDLKNEADMSDGTTGAMSSNKKVIYCTSLNWSADGSTLFSGYNDGVIRVWGI GRY 330 WD40repeat MSGVPAPPFATTTPENGTMSSNSPAFHRDSDDDDDQGEVFLDDSDIIHEVAVDD 227 1512protein EDLPDADDEADEAEEADDSLHIFTGHNGEVYSLACSPTDATLVATGAGDDKGFLWRIGHGDWAVELQGHKDSISSLAFSLDGQLLASGSLDGVIQIWDVPSGNLKGTLDGPGGGIEWIRWHPKGHIILAGSEDSTVWMWNADKMAYLNMFSGHGNSVTCGDFTPDGKTICTGSDDATLRIWNPKSGENIHVVKGHPYHAEGLTSMAISSDSGLAITGAKDGSVRIVNISSGRVVSSLDAHADSVEFVGLALSSPWAATGSLDQKLIIWDLQHSSPRATCDHEDGVTCLSWVGASRFLASGCVDGKVRVWDSLSGDCVRTFHGHSDAIQSLSVSANEEFLVSVSIDGTARVFEIAEFH 331 WD40 repeatMGTSQHQLSSCLQLLPRRRGNKNLIFRRTMASGGAAAVAPPPGYKPYRHLKTLT 33 1076 proteinGHVAAVSCVKFSNDGTLLASASLDKTLIIWSSAALSLLHRLVGHSEGVSDLAWSSDSHYICSASDDRTLRIWSSRSPFDCLKTLRGHTDFVFCVNFNPQSSLIVSGSFDETIRIWEVKTGRCLNVIRAHSMPVTSVHFNRDGSLIVSGSHDGSCKIWDTKNGACLKTLIDDTVPAVSFAKFSPNGKFILVATLNDTLKLWNYATGKFLKIYTGHKNSVYCLTSTFSVTNGKYIVSGSEDRCICIWDLQGKNLIQKLEGHSDTVISVTCHPSENKIASAGLDSDRTVRIWLQDA 332 WD40 repeatMPSQKIETGHQDIVHDVAMDYYGKRVATASSDTTIKIIGVSNSSGSQHLASLSG 65 973 proteinHKGPVWQVAWAHPKFGSILASCSYDGQVILWKEGNQNDWAQAHVFNDHKSSVNSIAWAPHELGLCLACGSSDGNISVFTARPDGGWDTTRIEQAHPVGVTSVSWAPSMAPGALVGSGLLDPVQKLASGGCDNTVKVWKLYNGTWKMDCFPALQMHSDWVRDVAWAPNLGLPKSTIASASQDGTVVIWTVAKEGEQWQGKVLKDFKTPVWRVSWSLTGNLLAVADGNNNVTLWNEAVDGEWQQVTTVEP 333 WD40 repeatMKIAGLKSVENAHDESVWAAAWVPATESRPALLLTGSLDETVKLWRPDELALER 82 1047 proteinTNAGHFLGVVSVAAHPSGVIAASASIDSFVRVFDVDTNATIATLEAPPSEVWQMQFDPKGTTLAVAGGGSASIKLWDTATWELNATLSIPRPEQPKPSEKGNKKFVLSVAWSPDGRRLACGSMDGTISIFDVARAKFLHHLEGHFMPVRSLVFSPVEPRLLFSASDDAHVHMYDSEGKSLVGSMSGHASWVLSVDVSPDGAALATGSSDRTVRLWDLSMRAAVQTMSNHSDQVWGVAFRPMAGAGVRAGGRLASVSDDKSISLYDYS 334 WD40 repeatMEIDLGNLAFDVDFHPSEQLVASGLITGDLLLYRYGDGSSPEKLLEVRAHGESC 43 1101 proteinRAVRFINDGKAILTGSPDCSILATDVETGSVVARVENAHEAAVNRLVNLTESTIATGDDNGCIKVWDTRQRSCCNTFSAHEDFISDMTFASDSMKLVVTSGDGTLSVCNLRSNKVQTRSEFSEDELLSVVIMKNGRKVVCGTQSGTLLLYSWGFFKDCSDRFVDLSPSSVDALLKLDEDRIIAGTENGLISLIGILPNRIIQPIAEHSDHPIERLAFSHDKKFLGSISHDQTLKLWDLNDILGSEDSPSSQAAIDDSDSDEMDVDANPPDSSKGNKKKHSGKGNDVGNANNFFADLGD 335 WD40 repeatMSQQPSVILATASYDHTIRFWEAKSGRCYRTIQYPDSQVNRLEITPHKRYLAVA 142 1095 proteinGNPSIRLFDVNSNTPQPVMSFDSHTNNVMAVGFQYDGNWMYSGSEDGTVRTWDLRARGCQREYESRGAVNTVVLHPNQTELISGDQNGNIRVWDLTANSCSCELVPEVDTAVRSLTVMWDGSLVVAANNNGTCYVWRLLRGSQTMTNFEPLHKLQAHNGYILKCLLSPEFCEPHRYLATASSDHTVKIWNVEGFTLEKTLIGHQRWVWDCVFSVDGAYLITASSDTTARLWSMSTGQDIRVYQGHHKATTCCALHDGAEGSPG 336 WD40 repeatMEDAMDMEVEVEVEAEEHSPSSSNPSGSSFRRFGLKNSIQTNFGSDYVFEITPK 61 1257 proteinFDWSLMGVSLSSNAVKLYSPTTGQYCGECRGHSDTVNGISFSGPSSPHVLHSCSSDGTIRAWDTRSFKEVSCISAGPSQEIFSFSFGGSSDSLLSAGCKSQILFWDWRNKKQVACLEDSHVDDVTQVCFVPHHQNKLISASVDGLICIFDTAGDINDDEHMESVINVGTSIGKVGIFGQTFEKLWCLTHIETLSVWDWKEGTNEANFEDARKLASDSWSLDHIDYFVDCHSAEEGEGLWVIGGTNAGTLGYFPVKYKGGAAIGSPEAVLGGGHSDVVRSVLPMSGMAGTTSKTRGIFGWTGGEDGRLCCWLSDDSSATSRSWMSSNLVLKSSRSHHKKNRHQPY 337 WD40 repeatMSQHQEYPMEYAADDYDVGEVEDDMYFHERVMGDSDTDEDEEYDHLDNKITDTS 193 1527 proteinAADARRGKDIQGIPWERLSVTREKYRRTRIEQYKNYENVPQSGESSEKDCKPTRKGGNYYEFWRNTRSVKSTILHFQLRNLVWSTTKHDVYLMSHFSIIHWSSLTCKKTEVLDVYGHVAPREKHPGSLLEGFTQTQVSTLAVRDKLLIAGGFQGELICKNLDRPGVSYCCRTTYDDNAITNAVEIYDYPSGAVHFMASNNDCGVRDFDMEKFELSRHFTFPWPVNHTSLSPDGKLLVIVGDNPEGIVVDSQRGKTIRPLQGHLDFSFASAWHPDGHIFATGNQDKTCRIWDIRNLSKSVAVLKGNLGAIRSIRFTSDGRFMAMAEPADFVHVYDVKSGYEKEQEIDFFGEISGVSFSPDTESLFVGVWDRTYGSLLQY NRCRNYSYLDSM 338WD40 repeat MGASSDPNPDVSDEHQKRSEIYTYEAPWHIYAMNWSVRRDKKYRLAIASLLDHP 1091155 protein AAAAAVPNRVEIVQLDDSTGEIRADPNLSFDHPYPATKAAFVPDKDCQRADLLATSSDFLRIWRIADDSSRVDLRSFLNGNKNSEFCRPLTSFDWNEAEPKRIGTSSIDTTCTIWDIERETVDTQLIAHDKEVYDIAWGGVSVFASVSADGSVRVFDLRDKEHSTIIYESSEPDTPLVRLGWNKQDPRYMATIIMDSAKVVVLDIRYPTMPVVELQRHQASVNAIAWAPHSSCHICTAGDDSQALIWDLSSMAQPVEGGLDPILAYTAGAEIEQLQWSSSQPDWVAIAFSLKLQ 339 WD40 repeatMRGGGGGGDATGWDEDAYRESVLKEREVQTRTVFRAAFAPSPSPSPSPDAVVVA 71 1213 proteinSSDGSVASYSISACLSDHRLQSLRFADAKSQNVLEAEPACFLQGHDGPAYDVKFYGEGEDSLLLSCGDDGRIRGWMWRDITSSEAHDHSQGNSAKPVLDLVNPQSRGPWGALSPIPENNALAVDVKRGSIYAAAGDSCAYCWDVECGKIKTVFKGHSDYLHCIAARNSSSQIITGSEDGTARIWDCRSGKCVQVIDPDKDHKKGFFASVSCLALDASESWLVCGRGRDLSVWSISASDCIAKISTNAPAQDVLFDDNQILLVGAEPLISRLDMNGAVLSQIHCAPQSVFSVSLHQSGVTAVGGYGGLVDVISQFGSHLCTFRCK CI 340 WD40repeat MEAPIIDPLQGDFPEVIEEYLEHGIMKCIAFNRRGTLLAAGCTDGSCIIWDFET 109 1785protein RGVAKELRDKECTAAITSVCWSKYGHRILVSASDKSLILWDVLSGEKIAHTTLQHTVLQACLHPGSSTPSICLACPFSSAPMIVDLNTGSTTALPVLTADVSNGATPLSRNKTSDTSVTYSPCNACFNKHGDLVYAGTSKGEILIIDHKNVRVCAIVLVSGGAVIKNVVFSRNGQYMLTNSNDRLIRIYKNLLPPKDGLKMLDELNESFNESDDVEKLKAIGSKCLELLHEFQDSITRVQWKAPCFSGDGEWVIGGAASRGEHKIYIWDRAGHLVKILEGPKEALMDLAWHPVHPIIISVSLTGLVYIWAKDYTENWSAFAPDFKELEENEEYVEREDEFDLVPETEKVKGLDVHEDDEVDVLTVERDSVFSDSDMSQEELCFLPAVPCLDIPEQQDKCVGSCSKLPDGNHSGSPLSVEAGQNGNASNHNSSPLEPMENSTADDTDGVRLKRKRKPSEKGLELQAEKVKKPVKPLKSSGRLSKTNKPVIDPDSSNGVYGDDGSD 341 WD40 repeatMRGVSWPEDGNNPSTSSSSQRNQQQAHAPRAVSGHAASHPSASNIFKLLVQREV 364 2685 proteinSPRSKHSSKKLWREASKCQPYPFQQSCEAVRDVRQGLISWVESASLRHLSAKYCPLVPPPRSTIAAAFSPDGKILASTHGDHTVKLIDSQTGSCLKVLRGHRRTPWVVRFHPLYPEILASGSLDHEVRLWDANTAECIGSRNFYRPIASIAFHARGELLAVASGHKLYIWHYNRRGETSSPTIVLRTQRSLRAVHFHPHAAPFLLTAEVNDLDSADSAMTLATSPGYLHYPPPTVYFADAHSHERSRLADELPLMPLPLLMWPSFTRDDGRVPLQRIDGDVGLNGQQRVDSSSSVRLWTYSTPSGQYELLLSPVESGNSPSMPEETGNNAFSSAVEAEVSQSAMDTVEDMEVQPEERNTQFFSFSDPRFWELPLLHGWLVGQTQAGPRSVRQSSPGDIETQSAFGEVASVSPITSGVMPVSMDPSRFGGRSGSRYRSPGSRGVHVTGPNNDGPRDENDPQSVVSKLRSELAASLAAAASTELPCTVKLRIWPHDVKDPCAQLDLESCRLTIPHAVLCSEMGAHFSPCGRFLAACVACVLPHLESDPGLHGQVNQDVTGVATSPTRHPISAHQIMYELRIYSLEEATFGIVLASRPVRAAHCLTSIQFSPTSEHLLLAYGRRHSSLLKSIVIDGENTVPIYTILEVYRVSDMELVRVLPSAEDEVNVACFHPSVGGGLIYGTKEGKLRILHYDSSHGLNLKSS GFLDENVPEVQTYALEC342 WD40 repeat MDSAVAIAALSLVVGAAIALLFFGNYFRKRRSEVVAMAEADLQPHPKNPSRPPP96 1412 protein QPAAKKVHAKSHAHGADKDKNKRHHPLDLNTLKGHGDSVTGLCFASDGRSLATACADGVVRVFKLDDASNKSFKFLRINLPAGGHPTAVAFGDGVSSVIVASQHLSGCSLYMYGEEKPTNLDSNKQQTKLPMPEIKWEHHKVHEQKAILTLSGAAANYDSGDGSTIIASCSEGTDIIIWHAKTGKILGNVDTNQLKNTMSAISPNGRFIAAAAFTADVKVWEIVYSKDGSVKGVTKVMQLKGHKSAVTWLCFTPNSEQIVTASKDGSIRIWNINVRYHLDEDTKTLKVFPIPLQDSSGTTLHYERLSLSPDGKILAATHGSMLQWLCIETGKVLDTAEKAHDGDITCMSWAPQSIPTGDKKVNVLATASGDKKVKLWA APPLPS 343 WD40repeat MEVEPKKASKTFPVKPKLKPKPRTPSGKTPESKYWSSFKTTHPLDNLSFSVPSL 116 1702protein AFSPSPPHLLAAAHSATVSLFSPHRTTISSFSDVVSSLSFRSDGQLLAASDLSGLIQVFDVRSRTPLRRLRSHARPVRFVRYPVLDKLHLVSGGDDALVKYWDVAGESVVSELRGHKDYVRCGDCSPADANCFVTGSYDHVVKLWDVRVRDGNRAATEVNHGSPVQDVIFLPSGSLVATAGGNSVKIWDLIGGGRMVYSMESHNKTVTSICVGTMGAQQSGEEGVQLRILSVGLDGYMKVFDYSRMKVTHSMRFPAPLLSIGFSPDSNVRAIGTSNGILYVGKRKAKENAEGGANGILGLGSVEEPRRRVLKPSFYRYFHRGQSEKPSEGDYLVMRPKKVKLAEHDKLLKKFQHKNALISVLGGNDPEKVVAVMEELVARRALLKCVLNLDADELGLILTFLHKNSTVPRYSSLLLGLAKKVIDLRLEDIRASDALKGHIRNLKRSVDEEIRIQEGLQEIQGMVSPLLRIAGRR 344 WD40 repeatMQGGSSGVGYGLKYQARCISDVKADTDHTSFLTGTLSLKEENEVHLLRLSSGGT 46 1101 proteinELICEGLFSHPSEIWDLSSCPFDQRIFSTVFSTGESYGAAVWQIPELYGQLNSPQLEKIASLDAHSRKISCVLWWPSGRHDKLVSIDEENIFLWGLDCSKKSAQVQSQESAGMLHNLSGGAWDPHDVNTVAATCESSIQFWDLRTMKKANSLESVHARDLDYDMRKKHLLVTSEDESGVRVWDLRMPKAPIQEFPGHTHWTWAVRCNPDYEGLILSAGTDSAVNLWWSSTASSDELISERLIDSPTRKLDPLLHSYNDYEDSVYGLAWSSREPWIFASLSYDGRVVVESVKPFLSRK 345 WD40 repeatMAEEEGSAELEQQLEEEFAVWKKNTPILYDLLISHALEWPSLTVHWAPLLPQPS 23 1258 proteinSSAAAAAGDPSLAAHRLVLGTHTSDGAPNFLILADALLPSSESDHCGDDAVLPKVEISQKIRVDGEVNRARFMPQNHNIVGAKTNGCEVYVFDCSKQAAKQHDGGFDPDLRLTGHDGEGYGLSWSPLKENYLLSASHDKKICLWDISAAAQDKVLGAMHVFEAHEGAVGDASWHSKNDNLFGSAGDDCQLMIWDLRTNKAQQCVKAHEKEVNSVSFNSYNDWILATASSDTTVGLFDMRKLTTPLHVFSSHEGEVLQVEWDPNHEAVLASSSEDRRVMVWDLNRIGDEQQEGDASDGPAELLFSHGGHKAKISDFSWNKNEPWVISSVAEDNSVQVWQMAESICGDDDDMQAMEGYI 346 WD40 repeatMGNYGEEDEDQYFDALEETASVSDRGSNSSDCCSSGSGLDENVLDSLGFEFWTK 404 2644 proteinFPESVRARRNRFLMLTGLGIEANSVDKEDAFPPSCNEIEVYTCKVTRDDGAVQRSLDSYNCISLLQSSTSIRSNQEVESLRGDSLLSSFRGRSKESDDLTELCGMGCPESKRNAVSEFGSVSQGSIEELRRIVASSPLVHPLLHRKLEYERELIETKQKMGAGWLRKFGSATCISGRQGDTWSDPDDLEITAGMKMRRVRAHSSKKKYKELSSLYAAQEFLAHEGSISTMKFSMDGQYLASAGEDTVVRVWKVTEEDRSERVNVTVDPSCLYFALNESTQLASLNTNKEHIGKAKTFQRSSDSSCVILPLKVFQITEKPWHEFKGHNGEVLDLSWSSKGYLLSSSTDKTVRLWRVGCDRCQRVYSHNDYVTCISFNPVNENFFISGSIDGKVRIWNVFGGQVVAYIDCREIVSAVCYRSDGKGAIVGTMTGNCLFYSIKDNHLQMDAQVYLHGKKKSPGKRITGFQFPPNDPGKLMITSADSVIRVLSGLDVVCKLKGPRNSGGPMIATFTSDGKHVISASEDSNVYIWNYAGQDKTSSRVKKIWSCESFWSSNASVALPWCGIRTVPEALAPPSRSEERRASCAENGENHHMLEEYFQKMPPYSPDCFSLSRGFFLELLPKGSATWPEEKLSDTSPPTVSSQAISKLEYKFLKSACHSVLSSAHMWGLVIVTAGWDGRIRTYHNYGLPVRS 347 WD40 repeatMDIDFKEYRLRCELRGHEDDVRGVCVCGDGSIGTSSRDRTVRLWAPSAGERRKY 107 2383 proteinEVARVLLGHKSFVGPLAWVPPSEELPEGGIVSGGMDTLVMAWDLRNGEAQTLKGHQLQVTGIVLDGGDIVSASVDCTLIRWKNGQLTEHWEAHKAPIQAVIRLPSGELVTGSSDTTLKLWRGKTCTQTFVGHTDTVRGLAVMPDLGILSASHDGSIRLWAVSGECLMEMVDHTSIVYSVDSHASGLIVSGSEDRFAKIWKDGVCFQSIEHPGCVWDVKFLEDGDIVTACSDGTIRIWTNQEDRMANSTELELFDLELSSYKRSRKRVGGLKLEELPGLEALQVPGTSDGQTKVIREGDNGVAYAWNSTELKWDKIGEVVDGPEDSMNRPALDGVQYDYVFDVDIGDGEPTRKLPYNRSDNPYDTADKWLLKENLPLSYRQQIVEFILANSGQRDFNLDPSFRDPYTGSSAYVPGAPSQLAAKQARPTFKHIPKKGMLVFDAAQFDGILKKINEFNNTLLSNQEKKNLSLTDIEISRLGAVVKILKDTSHYHSSKFADADFDLMLKLLESWPYEMMFPVIDIFRMVILHPDGADGLLRHQEDKKDVLMESIKRATGNPSVPANFLTSIRAVTNLFKNSAYYSWLQKHRSEMLDAFSSCSSSSNKNLQLSYATLLLNYAVLLIEKKDEEGQSQVLSAALELAENESLEVDARYRALVAIGSLMLDGLVKRIALDFDVEHIAKAARTSKEAKIAEVGADIELLIK QS 348 WD40repeat MEFTEAYKQSGPCCFSPNARFIAVAVDYRLVIRDTLSLKVVQLFSCLDKISYIE 243 1625protein WALDSEYILCGLYKRPMIQAWSLIQPEWTCKIDEGPAGIAYARWSPDSRHILTTSDFQLRLTVWSLVNTACVHVQWPKHASKGVSFTRDGKFAAICTRHDCKDYINLLSCHNWEIMGVFAVDTLDLADIQWSPDDSAIVIWDSPLEYKVLVYSPDGRCLFKYQAYESGLGVKSVSWSPCGQFLAVGSYDQMLRVLSHLTWKTFAEFTHLSNVRAPCCAAIFKEVDEPLQIDMSELSLSDDYMQGNSGDAPEGHYRVRYDVTEVPITLPCQKPPADRPNPKQGIGLMSWSNDSQYICTRNDSMPTILWIWDMRHLELAAILVQKDPIRAAVWDPTGTRLVLCTGSSHLYMWTPSGAYCVSVPLSQFNITDLKWNSDGSCLLLKDKESFCCAAAPLPPDESSDYSSDD 349 WD40 repeatMATIAALDDDMVRSMSIGAVFSDFVGKLNSLDFHRKDDILVTAGEDDSVRLYDI 126 1127 proteinANARLLKTTFHKKHGTDRVCFTHHPNSLICSSTKNLDTGESLRYISMYDNRSLRYFKGHKQRVVSLCMSPINDSFMSGSLDHSVRMWDLRVNACQGILRLRGRPTVAYDQQGLVFAVAMEGGAIKLFDSRSYDKGPFDAFLVGGDTSEVCDIKFSNDGKSVLLSTTNNNIYVLDAYAGDKQCGFNLEPSPSTPIEASFSPDGQYVVSGSGDGTLHAWNISRRNEVACWNSHIGVASCLKWAPRRAMFVAASTVLTFWIPNSEPELASAKG EAGVPPEQV 350WD40 repeat MSVAELKERHRAATETVNSLRERLKQKRVQLLDTDVAGYARTQGKTPVTFGATD 2571390 protein LVCCRTLQGHTGKVYSLDWTPERNRIVSVSQDGRFIVWNALTSQKTHAIRLPCAWVMTCAFAPNGQSVACGGLDSVCSIFNLNSPVDRDSNLPVSRMLSGHKGYVSSCQYVPDGDAHLITGSGDQTCVLWDITTGLRTSVFGGEFQSGHTADVLSVSTNGSSPRIFVSGSCDSTARMWDTRVASRAVHTYHGHESGVNAVKFFPDGNRFGTGSDDGTCRLFDIRTGHELQVYYQQRGIDEIPHVTSIAFSISGRLLIAGYSNGDCFVWDTLLAQVVLNLGSLQNSHEGRISCLGVSADGSALCTGSWDTNLKIWAFGGIRRVT 351 WD40 repeatMKKRPRGASLDQAVVDIRRREVGGLSGLSFARRLAASEGLVLRLDIYNKLKGHR 178 1632 proteinGCVNTVGFNLDGDIVISGSDDRHVKLWDWQTGKVKLSFDSGHLSNVFQAKIMPYTDDRSIVTCAADGQARHAQILEGGQVQTMLLAKHRGRAHKLAIDPGSPHIVYTCGEDGLVQRLDLRSNTARELFTCREVYGTHVEVVHLNAIAIDPRNPNLFVIGGSDEYARVYDIRNYKWNGSHNFGRSANYFCPSHLIGEAHVGITGLAFSGQSELLVSYNDESIYLFTQEMGLGPDPLSASTKSVDSNSSEVTSPTAVNVDDNVTPQVYKGHRNCETVKGVGFFGPKCEYVVSGSDCGRIFIWKKKGGQLIRVMAADKHVVNCIEPHPHIPALASSGIENDIKIWTPKAIERATLPMNVEQLKPKARGWMNRISSPRQLLLQLYSLERWPEHGGETSSGLAAGQEELTELFFALSANGNGSPDGGGDPSGPLL 352 WD40 repeatMSKRGYKLQEFVAHSSNVNCLSIGKKACRLFLTGGDDCKVNLWAIGKPNSLMSL 290 2917 proteinCGHTNAVESVAFDSAEVLVLAGASSGVIKLWDVEEAKMVRGLTGHRSNCTAMEFHPFGEFFASGSTDTNLKIWDIRKKGCIHTYKGHTRGISTIRFSPDGRWVVSGGNDNVVKVWDLTAGKLLHDFKFHENHIRSIDFHPLEFLLATGSADRTVKFWDLETFELIGSSRPEAAGVRAIAFHPDGRTLFCGLEDSLKVYSWEPVICHDGVDMGWSTLADLCIHDGKLLGCSYYQSSVGVWVADASLIEPYGTNVKPQQKDSGDDEIEHQESRPSAKVGTTIRSTSIMRCASPDYETKDIKNIYVDTASGNPVSSQRVGTTNFAKVTQPLDFNDTPNLTLRRQGLVTETPDGLSGHVPSKSITQPKVVSRDSPDGKDSSRRESITFSRTKPGMLLRPAHSRRPSSTKYDVDRLSACAEIGVLSSAKSGSESLVDSFLNIKVAPEDGARNGCEDNHSSVKNVSVESEKVLPLQTPKTEKCDQTVGFKEEINSVKFVNGVAVVPGRTRTLVEKFEKREKLNSTEDQTINTPENPTLDKTPPPSLAENEEKSDRLNIVERKATRMSSHMVTAEDRTPVTLVGSPEDQSTVMAPQRELPADESSKTPPLPVEDLEIHHGSNVSEDKATILSSQTVSEEDSKRSTLIRNFRRRDRFKSTEGRSPVMATQRKLPTDESGKTSSLPMEDLEIKGGLNVSEDKATSFSSRAPPREDRAHSALVRNVRKRDKFKSTNDTITVMVHQRGLSTDEASTVSVERVERRQLSNNVENPLNNLPPHSVPPTTTRGEPQYVGSESDSVNHEDVTELLLGNHEVFLST LRSRLTKLQVV 353WD40 repeat MSTFLTGTALSNPNPNKSYEVVQPPNDSVSSLSFNPKANFLVATSWDNQVRCWE 1481197 protein IVRSGTSLGTTPKASISHDQPVLCSTWKDDGTTVFSGGCDKQVKMWPLSGGQPMTVAMHDAPIKEISWIPEMNLLVTGSWDKTLRYWDTRQANPVHIQQLPERCYALTVRHPLMVVGTADRNLIIYNLQSPQTEFKRISSPLKYQTRCLAAFPDQQGFLVGSIEGRVGVHHLDDSQQSKNFTFKCHREGSEIYSVNSLNFHPVHHTFATAGSDGAFNFWDKDSKQRLKAMSRCSQPIPCSTFNNDGSIFAYSACYDWSKGAENHNPATAKTYIFLHLPQESEVKGKPRLGTTGRK 354 WD40 repeatMEVEAQQRDVNNVMCQLVDPEGTTLGPPMYLPQDVGPQQLQQMVNKLLSNEDKL 140 1567 proteinPYTFYISDQELVVPLESYLQKNKVSVEKVLSIVYQPQAIFRIRPVNRCSATIAGHSEAVLSVAFSPDGKQLASGSGDTTVRLWDLSTQTPMFTCKGHKNWVLSIAWSPDGKHLVSGSKAGEIQCWDPLTGQPSGNPLVGHKKWITGISWEPVHLSSPCRRFVSSSKDGDARIWDVTLRRCVICLSGHTLAVTCVKWGGDGVIYTGSQDCTIKVWETSQGKLIRELKGHGHWVNSLALSTEYVLRTGAFDHTGKQYSSAEEMKQVALERYKKMKGNAPERLVSGSDDFTMFLWEPSVSKHPKTRMTGHQQLVNHVYFSPDGQWVASASFDKSVKLWNGITGKFVAAFRGHVGPVYQISWSADSRLLLSGSKDSTLKIWDIRTKKLKRDLPGHADEVFAVDWSPDGEKVVSGGKDKVLKLWMG 355 WD40 repeatMDAGSAHSSSNMKTQSRSPLQEQFLQRRNSRENLDRFIPNRSAMDFDYAHYMLT 376 1737 proteinEGRKGKENPAVSSPSREAYRKQLAETLNMNRTRILAFKNKPPTPVELIPHELTSAQPAKPTKTRRYIPQTSERTLDAPDLLDDYYLNLLDWGSSNVLSIALGNTVYLWNASDGSTSELVTIDDETGPVTSVSWAPDGRHIAVGLNNSDVQLWDSADNRLLRTLRGGHRSRVGSLAWNNHILTTGGMDGLIVNNDVRVRSHIVDTYRGHTQEVCGLKWSASGQQLASGGNDNILHIWDRSTASSNSPTQWLHRLEEHTAAVKALAWCPFQGNLLASGGGGGDRTIKFWNTHTGACLNSVDTGSQVCALLWNKNERELLSSHGFTQNQLTLWKYPSMVKIAELTGHTSRVLFMAQSPDGCTVASAAGDETLRFWNVFGVPEVAKPAPKANPEPFAHLNRIR 356 WD40 repeatMEEAIPFKNLPSREYQGHKKKVHSVAWNCTGTKLASGSVDQTARVWHIEPHGHG 69 1010 proteinKVKDIELKGHTDSVDQLCWDPKHADLIATASGDKTVRLWDARSGKCSQQAELSGENINITYKPDGTHVAVGNRDDELTILDVRKFKPIHKRKFNYEVNEIAWNMSGEMFFLTTGNGTVEVLAYPSLRPVDTLMAHTAGCYCIAIDPVGRYFAVGSADSLVSLWDISEMLCVRTFTKLEWPVRTISFNHTGDYVASASEDLFIDISNVQTGRTVHQIPCRAAMNSVEWNPKYNLLAYAGDDKNKYQADEGVFRIFGFESA 357 WD40 repeatMGKDEEEMRGEIEERLINEEYKVWKKNTPFLYDLVITHALEWPSLTVEWLPDRE 149 1423 proteinEPPGKDYSVQKLVLGTHTSENEPNYLMLAQVQLPLEDAENDARHYDDDRADVGGFGCANGKVQIIQQINHDGEVNRARYMPQNSFIIATKTVSAEVYVFDYSKHPSKPPLDGACSPDLRLRGHSTEGYGLSWSKFKQGHLLSGSDDAQICLWDINATPKNKSLDAMQIFKVHEGVVEDVAWHLRHEYLFGSVGDDQYLLIWDLRTPSVTKPVQSVVAHQSEVNCLAFNPFNEWVVATGSTDKTVKLFDLRKISTALHTFDAHKEEVFQVGWNPKNETILASCCLGRRLMVWDLSRIDEEQTPEDAEDGPPELLFIHGGHTSKISDFSWNTCEDWVVASVAEDNILQIWQMAENIYHDEDDVPGEESNKGS 358 WD40 repeatMMRGFSCTEDGDAPSTSSTSPPPPPPPPHRQQMQAPRASSSSSGQPTSRRSTGN 365 2677 proteinVFKLLARREVSPRSKHSLKKFWGEASECQLCPFQQSYEAVRDVRRSLISWVEAFSLQHLSAKYCPLMPPPRSTIAAAFSPDGKILASTHGDHTVKLIDSQTGSCLKVLRGHRRTPWVVRFHPLYPEILASGSLDHEVHLWDANTAECIGSRNFYRPIASIAFHAQGDLLAVASGHKLYIWHYNRSGETSSPTIVLRTPRSLRAVHFHPHAAPFLLTAEVNDLDLTDSAMTLATSPGYLHYPPPTIYLADAHSNERSRLEDELPLMPSPLLMWPSFTRDDGRATLPHIGGDVGLSGQQRVDSLSSSQYEFHPSPIEPSSSTSMHEEMGTDPFSSVRESEVTQSAMNIVDNTEVQPEERSTYSFSFSDPRFWELPSVYGWLVGQTQAAPRTAPSPGALETASALGEVASVSPVRSEFMPGGMDQPRLGGRSGSGCRSSGSRMMRTAGLNDHPHDENYPQSVVSKLRSELEASLAAAASTELPCTVKLRVWPYDMKDPCALFRSESCRLTIPHAVLCSEMGAHFSPCGRFFAACVACVLPQLEADPVLHGQVDPDVTGVATSPTRHPVSAYQIMYELRIYSLEEATFGMVLASRSIRAAHCLTSIQFSPTSEHLLLAYGRRHNSLLKSIVIDGENTVPIYSILEVYRVSDMELVRVLPSAEDEVNVACFHPSVGGGLVYGTKEGKLRILQIDSSGGLNPKSTGFL DENMAEVPTYALEC359 WD40 repeat MGEGDLPRTEAGVLRGHEGAVLAARFNGDGNYCLSCGKDRTIRLWNPHRGIHIK24 923 protein TYKSHGREVRDVHCTSDNSKLISCGGDRQIFYWDVSTGRVIRRFRGHDSEVNAVKFNDYASVVVSAGYDRSVRAWDCRSHSTEPIQIINTFQDSVMSVCLTKTEIIGGSVDGTVRTFDIRIGREISDDLGQPVNCISMSNDGNCILASCLDSTLRLVDRSAGELLQEYKGHTCKSYKLDCCLTNTDAHVAGGSEDGYVFFWDLVDASVISKFRAHSSVVTSVSYHPKEDCMITASVDGTIKVWKT 360 WD40 repeatMACIKGVGRSASVAMAPDGGYLATGTMAGTVDLSFSSSASLEIFGLDFQSDDRD 221 3598 proteinLPLIAESPSSERFNRLSWGKNGSGSDEFSLGLIAGGLVDGTIGLWNPLSLIRSEAGDKAIVGHLSRHKGPVRGLEFNVIAPNLLASGADDGEICIWDLAAPREPSHFPPLRGSGSAAQGEISFLSWNSKVQHILASTSYNGTTVVWDLKKQKPVISFSDSVRRRCSVLQWNPDLATQLVVASDEDSSPTLRLWDMRNIMSPVKEFAGHTRGVIAMSWCPNDSSYLVTCAKDNRTICWDTVTGEIVCELPAGSNWNFDVHWYPKIPGVISASSFDGKIGIYNVEGCSRYGVRENEFGAATLRAPKWFKRPVGASFGFGGKVVSFHTRSTGGPSVNSSEVFVHDIITEQTLVSRSSEFEAAIQSGDRPSLRALCEKKSQHCESTDDQETWGFLKVLLEDDGTARSKLLAHLGFDIPTETNDGSQEDLSQQVNALGLEDVTADKVVQEDNNESMVFPTDNGEDFFNNLPSPRADTPVSTSADGFPTVNAAVEPSQDEVDGLEESSDPSFDDSVQRALVVGDYKAAVALCMSANKLADALVIAHVGGASLWESTRDKYLKMSRLPYLKVVFAMVNNDLQSLVDTRPLKFWKETLAILCSFAQGEEWAMLCNSLASKLMAAGNMLAATLCFICAGNIDKTVEIWSRSLATEHDGMSYMDLLQDLMEKTIVLALASGQKQFSASVCKLVEKYAEILASQGLLTTAMDYLKLLGTDDLSPELAVLRDRIAFSVEAEKGANISAFNGSQDPRGAVYGVDQSNYGMVDTSQHYYPEAAQPQVPHTVPGSPYGENYQQPFGSSFGKGYNTPMQYQAPSQASMFVPSEPPQNAQPSFVPTPVTSQPTTRSQFIPAPPLALRNPEQYQQPTLGSHLYPGSVNPTFQPLPHAPGPVAPVPPQVSSVPGQNMPQAVAPTQMRGFMPVTNPGVVQNPGPISMQPATPIESAAAQPVVSPAAPPPTVQTADTSNVPAPQKPVIATLTRLYNETSEALGGSRANPAKKREIEDNSRKIGALFAKLNSGDISKNAADKLVQLCQALDNGDYSTALQIQVLLTTSEWDECNFWLATLKRMIKTRQNVRLS 361 WD40 repeatMKERGKGAGRSVDERYTQWKSLVPVLYDWLANHNLVWPSLSCRWGPQLEQATYK 44 1447 proteinNRQRLYLSEQTDGSVPNTLVIANVEVVKPRVAAAEHISQFNEEARSPFVKKFKTIIHPGEVNRIRELPQNSKIVATHTDSPDVLIWDVETQPNRHAVLGASTSRPDLILTGHKDNAEFALAMSPTEPFVLSGGKDRYVVLWSIQDHISTLAADPGSAKSPGSAGTNNKQSSKAAGGNDKTGDSPSIEPRGVYLGHGDTVEDVTFCPSSAQEFCSVGDDSCLILWDARTGSSPAIKVEKAHHADLHCVDWNPHDVNLILTGSADNTVRMFDRRNLTSGGVGSPVHTFEGHNAAVLCVQWSPDKSSVFGSSAEDGILNIWDHEKIGRKIETVGSKVPNSPPGLFFRHAGHRDKVVDFHWNSSDPWTIVSVSDDGESTGGGGTLQIWRMIDLIYRPEEEVLAELDKFKSHILSCTS 362 WD40 repeatMAKIAPGCEPVAGTLTPSKKREYRVTNRLQEGKRPLYAVVFNFIDSRYFNVFAT 196 1314 proteinVGGNRVTVYQCLEGGVIAVLQSYIDEDKDESFYTVSWACNIDRTPFVVAGGINGIIRVIDAGNEKIHRSFVGHGDSINEIRTQPLNPSLIVSASKDESVRLWNVHTGICILIFAGAGGHRNEVLSVDFHPSDKYRIASCGMDNTVKIWSMKEFWTYVEKSFTWTDLPSKFPTKYVQFPVFIAPVHSNYVDCNRWLGDFVLSKSVDNEIVLWEPKMKEQSPGEGSVDILQKYPVPECDIWFIKFSCDFHYHSIAIGNREGKIYVWELQSSPPVLIAKLSHPQSKSPIRQTAMSFDGSTILSCCEDGTIWRWDAITASTS 363 WD40 repeatMNTAMHFGAGWRSIAEMGYTMSRLEIEPESCEDEKSLDGVGNSQGPNELPRCLD 193 1668 proteinHELAHLTNLKSRPHEHLIRDFPGRRALPVSTVKMLAGRECNYSRRGRFSSADCCHMLSRYVPVNGPSPLDQMNSRAYVSQFSADGSLFVAGFQGSHIRIYNVDKGWKCQKNILTKSLRWTITDTSLSPDQRYLVYASMSPIVHIVDIGSAAMDSLANITEIHEGLDFSADSGPYSFGIFSVKFSTDGREVVAGSSDDSIYVYDLVANKLSLRIPAHESDVNTVCFADESGHIIYSGSDDTYCKVWDRRCLSARNKPAGVLMGHLEGITFIDSRGDGRYFISNGKDQTIKLWDIRKMGSDICRRGFRNFEWDYRWMDYPPRARDSKHPFDLSVATYKGHSVLRTLIRCYFSPVHSTGQKYIYTGSHDSCVYIYDVVTGAQVAALKHHKSPVRDCSWHPEYPMIVSSSWDGDIVKWEFFGNGETEIPAMIKKRIR RRHLY 364 WD40repeat MEPQPQAPKKRGRKPKPKEDKKEEQLHQPPPPPPPQQQAAPAPAPAATRSSTSG 78 1634protein SAGGRDRRPQQQHAVDEKYARWKSLVPVLYDWLANHNLLWPSLSCRWGPQLEQATYKNRQRLYISEQTDGSVPNTLVIANCEVVKPRVAAAEHVSQFNEEARSPFIRKYKTIIHPGEVNRVRELPQNPNIVATHTDSPDVLIWDVESQPNRHAVYGATASRPNLILTGHQENAEFALAMCPAEPFVLSGGKDKTVVLWSIQDHITASATDQTTNKSPGSGGSIIKKTGEGNEETGNGPSVGPRGIYCGHEDTVEDVAFCPSTAQEFCSVGDDSCLILWDARVGTNPVAKVEKAHNGDLHCVDWNPHDNNLILTGSADNSVNMFDRRNLTSNGVGSPVYKFEGHKAAVLCVQWSPDKPSVFGSSAEDGLLNIWDYERVDKKVDRAPNAPAGLFFQHAGHRDKIVDFHWNAADPWTMVSVSDDCDTAGGGGTLQIWRMSDLIYRPEEEVLAELENFKAHVLECSKA 365 WD40 repeatMGIFEPYRAVGYITTGVPFSVQRLGTETFVTVSVGKAFQVYNCAKLSLVLVGPQ 85 2826 proteinLPKKIRALASYREYTFAAYGSDIGIFKRAHQLATWSGHTAKVCLLLLFGEHILSVDVDGNAYIWAFKGMNYNLSPVGHILLDSNFTPSCIMHPDTYLNKVILGSQEGPLQLWNISTKTKLYEFKGWNSSVSSCVSSPALDVVAVGCADGKIHVHNIRYDEELVTFSHSMRGSVTALSFSTDGQPLLASGSSSGVVSIWNLDKRRLQSVIRDAHDGSIISLHFFANEPVLMSSSADNSIKMWIFDTSDGDPRLLRFRSGHSAPPLCIRFYANGRHILSAGQDRAFRLFSVVQDQQSRELSQRHVSKRAKKLKLKEEEIKLKPVIAFDVAEIRERDWCNVVTSHMDTPQAYVWRLQNFVIGEHILRPCPNKPTPVKACMISACGNFAILGTAGGWIERFNLQSGISRGSYIDQLEGTNSAHDGEVVGVACDATNTLMISAGYAGDIKVWDFKGRELKSRWEIGSSLVKISYHRLNGLLATVADDFIIRLFDAVALRMVRKFEGHTDRITDLCFSEDGKWLLSSSMDGSLRIWDIILARQVDAVFVDVSITALSLSPNMDILATTHVDQNGVFLWVNQSMFSGDSDINLYASGKEVVTVKLPSVSSVEGSQVEESNEPTIRHSESKDVPSFRPSLEQIPDLVTLSLLPKSQWQSLINLDIIKVRNKPVEPPKKPEKAPFFLPSIPSLSGEILFKPSEMSDKGDMKADEDKSKITPEVPSSRFLQLLHSCSEAKNFSPFTTYIKGLSPSTLDLELRMLQIIDDDAVDADADDPQDVDKRQELLSIELLMDYFIHEISCRSNFEFVQALVRLFLKIHGETIRRQSVLQNKAKVLLETQCSVWQRVDKLFQGARCMVAFLSNSQF 366 WD40 repeatMEETKVTCGSWIRRPENVNLAVLGRSPRRRGSAALEIFAFDPKSTSLSSSPLVA 74 1246 proteinHVIEEIEGDPLAIAVHPNGEDIVCFASSGSCLSFELSGQESNLKLLTKELPPLRGIGPQKCMAFSVDGSRFATGGVDGRLRILEWPSLRIILDEPKAHKSIRDLDFSLDSEFLATTSTDGSARIWKAEDGLPCTTLTRRSDEKIELCRFSKDGTKPFLFCTVQRGDKAVTGVWDISTWNKIGHKRLLRKPAVVMSISLDGKYLAQGSKDGDMCVVEVKKMEVSHWSKRLHLGTSLTSLEFCPIERVVITTSDEWGVLVTKLNVPADWKAWQVYLLLLGLFLASLVAFYIFYENSDSFWGFPLGKDQPARPKIGSVLGDPKSADD QNMWGEFGPLDM 367WD40 repeat MADPVEHQHQQHQQHQLQQQRRRGWRIQGGQYLGEISALCFLHLPPPPLSLSSS 1004377 protein PVLSLSSGLDSESRDRPACSFRFPSAGSGSQVSLFDLASGAMVRTFYVFRGIRVHGIVLGCADFPGGSSSSSSTLDYVIAVYGERRVKLFRLSVRLGRGAGEGSGTVLSADLELVSAAPRLSHWVMDVRFLKENGTSEDELQRCLTVAIGCSDNSIRLWDVDKCSFVLAVSSPERCLLYSMRLWGDNLEDLQVASGTIYNEILIWKVVPNHDAPSSNELTEEGLTNSCAGNSVHECLRYEAYHICRLVGHEGSIFRIAWSSDGSKLVSVSDDRSARIWEVHCKVQYSEDAGEVGLLFGHSARVWDCYISDNLIVTAGEDCSCRVWGLDGQQHDVIKEHIGRGIWRCLYDPWSSLLVTGGFDSAIKVHKLDASLAEASAKQSNIKDLSDGTELFTTHLPNSSGHSGHMDSKSEYVRCLSFSCEDVMYIATNHGYLYHAKLCNDGDLRWTELAQVSNEVQIICMELLPSNPYDPRIDADDWVAVGDGKGWTTVVRVVKNSDSPKVSTSFSWAAEMDRQLLGIHWCKSLGHRFIFTADPRGALKLWRFFEVSQSSSLYPENSPRISLIAEFKSDLGARIMCLDVAFESELLICGDLRGNLVLFPLLKDLLLDTFVVSAAKISPVNHFKGAHGISAVSSISVAHMSFNHIELRSTGADGCICYMEYDKGLQSLNFVGMKQVKELSMIESVSTENESTGYRTSGSYASGFASTDFIIWNLVTEAKVLQVSCGGWRRPHSYYLGDVPEMKNCFAYVKDDIIYIRRHWIKDSKDKILPQNLRLQFHGREVHSLCFVTGDFQLRKNKQSSWIVTGCEDGTVRLTRYTQCTDNWSSSKLLGEHVGGSAVRSICCVSNIHTTSSGTSVSDVKGIENLPKDIKGTLMEDECNPSLLISVGAKRVLTSWLLRRRKQDGKEDDVTDLQEAENSSLPSSAGSSTFSFQWLSTDMPVKYSVPSKKSGSIKKLIGVSDTNVRCKSLLPDSEALQSKVSAVDKNEDDWRYLAVTAFLVRHSGSRLIVCFIIVACSDATLAIRALVLPYRLWFDVALMVPLSSPVLSLQHVIIGRCQLPDENVQIGNVYVVISGATDGSIAFWDLTESVEAFMRRLSNIHLEKFMDCQKRPRTGRGSQGGRWWRSLSKIACKEQPINDPVTAKAIKELNRKLTGGVACGSSSSMLDASPELDSNAANSSFEIIEVNPFHVLNGVHQSGVNCLHVCETKHGQSSDGRFLYQLVSGGDDQALHLLKFEVLVQPPVQVPDVPNSDIRNSILVEEFLLDEQNQKTKCTIEFISQEKIASAHNSAVKGVWTDGTWVFSTGLDQRVRCWISKDRGTPTELAHFIISVPEPEALDARSICWDQYQIAVAGRGMQMIEFHVPSSEIR 368 WD40 repeatMPYKLSATLSNHSSDVRAVASPSDDLILSASRDSTAISWFRQSPSSFTPASVIR 58 2439 proteinAGSRFVNAIAYLPPTPRAPQGYAVVGGQDTVVNVFALGPGDKEEPEYTLVGHTDNVCALSVNSDDTIISGSWDKTAKVWKDFALVYDLKGHQQSVWAVLAMNEKEFLTASADRTIKYWVQHKTMQTYEGHRDAVRGLALIPDIGFASCSNDSEIRVWTMGGDVVYTLSGHTSFVYSLSVLPNGDLVSAGEDRSVRVWRDGECSQVIVHPAISVWAVSTMPNGDIISGSSDGVVRVFSESEKRWATASELKALEDQIASQSLPSQQVGDVKKTDLPGPEALSVPGKKAGEVKMIRSGDVVEAHQWDSLASSWQKIGEVVDAIGSGRKQLHDGKEYDYVFDVDIQEGAPPLKLPYNVSENPYTAAQRFLEQNDLPTGYLDQVVKFIEQNTAGVKLGNDGYVDPFTGASRYQPATQSTSNTASSSYMDPFTGGSRHIAESAPSNVPQGSHATGIIPFSKPIFFKLANVSAMQAKMFQFDEVLRNEISTATLAMRPDEVIMVNETFTYLSKVVTSTSSARTSLGWIHIETIMQILDRWPVPQRFPVIDLGRLVTAYCMNAFSGPGDLEKFFSCLFRTSEWTSITSGSKALTKAQETNVLLLFRTIANSLDGAPLNDMEWIKQIFRELAQTPQLVLNKSHRLALASVLFNFSCIGLKGPVPADVRTLHLTIILQVLRSPNDDPEVAYRTCVALGNMLYSDKTRGTPRDAQSPSPTELKSAVAAIKGGFSDPRINDVHREIMSLI 369 WD40 repeatMPPQKIESGHKDTVHDLAMDYYGKRLATASSDHTINVVGVSSSGSQHLATLIGH 159 1064 proteinQGPVWQISWAHPKFGSLLASCSYDGRVIIWREGNPNEWTQAQVFEEHKSSVNSVAWAPHELGLCLACGSSDGNISVFTARQDGGWDTSRIDQAHPVGVTSVSWAPSTAPGALVGSGMMEPVQKLCSGGCDNTVKVWKLYNRVWKLDCFPVLQMHTDWVRDVAWAPNLGLPKSTIASASQDGRVIIWTLAKEGDQWQGKVLYDFRTPVWRVSWSLTGNILAVADGNNNVSLWNEAVDGEWIQVSTVEP 370 WD40 repeatMSAPMLEIEARDVVKIVLQFCKENSLHQTFQTLQSECQVSLNTVDSIETFVADI 118 1665 proteinNSGRWDAILPQVAQLKLPRNTLEDLYEQIVLEMIELRELDTARAILRQTQAMGVMKQEQPERYLRLEHLLVRTYFDPNEAYQDSTKEKRRAQIAQALAAEVTVVPPSRLMALVGQALKWQQHQGLLPPGTQFDLFRGTAAMKQDVDDMYPTTLSHTIKFGTKSHAECARFSPDGQFLVSCSVDGFIEVWDYMSGKLKKDLQYQADETFMMHDDPVLCVDFSRDSEMLASGSQDGKIKVWRIRTGQCLRRLERAHSQGVTSVLFSRDGSQLLSTSFDGSARIHGLKSGKQLKEFRGHSSYVNDAIFSNDGSRVITASSDCTVKVWDVKTSDCLQTFKPPPPLRGGDASVNSVHLFPKNADHIVVCNKTSSIYIMTLQGQVVKSLSSGKREGGDFVAACVSPKGEWIYCVGEDRNLYCFSCQSGKLEHLMKVHEKDVIGVTHHPHRNLVATYSEDSTMKLWKP 371 WD40 repeatMDLLQSYAEDNDGDLGRHSSPEPSPPRLLPSKSAAPKVDDTTLALTVAQTNQTL 57 16828 proteinARPIDPSQHAVAFNPTYDQLWAPICGPAHPYAKDGIAQGMRNHKLGFVEDAAIGSFLFDEQYNTFQRYGYAADPCASTGNEYVGDLDALKQNDGISVYNIRQQEQKKYAEEYAKKKGEERGEGGREKAEVVSDKSTFHGKEERDYQGRSWIAPPKDAKATNDHCYIPKRLVHTWSGHTKGVSAIRFFPKHGHLILSAGMDTKVKIWDVFNSGKCMRTYMGHSKAVRDISFCNDGTKFLTAGYDKNIKYWDTETGKVISTFSTGKIPYVVKLHPDDEKQNILLAGMSDKKIVQWDMNTGQITQEYDQHLGAVNTITFVDDNRRFVTSSDDKSLRVWEFGIPVVIKYISEPHMHSMPSISLHPNTNWLAAQSLDNQILIYSTRERFQLNKKKRFAGHIVAGYACQVNFSPDGRFVMSGDGEGRCWFWDWKSCKVFRTLKCHEGVCIGCEWHPLEQSKVATCGWDGLIKYWD 372 WD40 repeatMESNGNLEQTLQDGRIYRQLNSLIVAHLRDHNFPQAASAVALATMTPLNVEAPR 250 1566 proteinNRLLELVAKGLAVEKGELLRGVSHAGTNDLGGSIPASYGLVPAPWTAIDFSSLRDTKGMSKSFTKHETRHLSDHKNVARCARFSTDGRFFATGSADTSIKLFEVSKIKQMMLPDSTDGAIRAVIRTFYDHTHPVNDLDFHPQNTVLISAAKDHTVKFFDYSKATAKRAFRVIQDTHNVRSVAFHPSGDFLLAGTDHPIPHLYDVNTFQCYLSANVPEFAVNAAINQVRYSSSGGMYVTASKDGTIRFWDGASANCVRSIAGAHGAAEVTSANFTKDQRYVLSCGKDSTVKLWEVGTGRLVKQYLGATHMQLRCQAVFNNTEEFVLSIDEPSNEIVVWDAMTAEKVARWPSNHNGPPRWIEHSPTEAAFVSCGTDRSIR FWKETH 373 WD40repeat MSNFQGEDGEYVADDFEAEDGDEELHGRESADPESDVDEIDTPSNRFTDTTADQ 106 1434protein ARRGRDIQGIPWERLSITREKYRRTRLEQYKNYENVPQSGEKSGKDCTVTEKGNSFYEFRRNSRSVKSTILHFQLRNLVWATSKHDVYLMSNYSVVHWSSLTGKKSEVLNLAGHVAPNEKHPGSLLEGFTQTQVSTLAVKDRFLVAGGFQGELICKFLDRPGISFCSRTTYDDNAITNAVEIYVSPSGGIHFIASNNDCGVRDFDMENFELSKHFRFPWPVNHTSLSPDGKLLVIVGDDPEGILVDAKTGKTIMPLRGHLDFSFASEWHPDGVTFATGNQDKTCRIWDIRNLSKSIAVLKGNLGAIRSIRYTSDGRYMAIAEPADFVHVYDTKTGYKKEQEIDFFGEISGMSFSPDTESLFIGVWDRTYGSLLEYGRR RNFSYLDCLV 374WD40 repeat MGVEEDLEDLNALAESTDAAVDGQAALASAVDSVTLQPAPPILPPVIPPPAVPV 1901917 protein VAPVPTIPPVLRPLAPLPIRPPVLRPPAPKRDEAGSSDSDSDHDGTAAGSTAEYEITEESRLVRERHEKAMQDLMMKRRGAALAVPTNDKAVRARLRRLGEPMTLFGEREMERRDRLRMLMAKLDAEGQLEKLMKAHEDEEAAASAAPEDVEEEMLQYPFYTEGSKALFNARIDIAKFSITRAALRLERARRRRDDPDEDVDAEIDWALKKAESLSLHCSEIGDDRPLSGCSFSHDGKLLATCSMSGVAKLWDTCRMPQVNRVLTLKGHTERATDVAFSPVQNHIATASADRTAKLWNTEGTILKTFEGHLDRLGRIAFHPSGKYLGTTSFDKTWRLWDIESGEELLLQEGHSRSIYGIDFHRDGSLVASCGLDALARVWDLRTGRSILALEGHVKPVLGVSFSPNGYHLATGGEDNTCRIWDLRKKKSLYTIPAHANLISEVKFEPQEGYFLVTASYDTTAKVWSARDFKPVKTLSVHEAKITSVDITADASHIVTVSHDRTIKLWTSNDDVKEQAMDVD 375 WD40 repeatMVKAYLRYEPAAAFGVIASVESNIAYDASGKHLLAPALEKVGVWHVRQGVCTKA 102 2942 proteinLAPSASSAAGPSLAVTAIASSPSSLIASGYADGSIRIWDFEKGSCETTLNGHKGAVSVLRYGKLGSLLASGSKDNDIILWDVVGETGLYRLRGHRDQVTDLVFLDSDKKLVSSSKDKYLRVWDLETQHCMQIVGGHHSEIWSLDTDPEERYLVTGSADPELRFYTVKNDSSDERSEADASGGVGNGDLASHNKWDVLKQFGEIQRQSKDRVATVRFNKNGNLLACQAAGKLVEVFRVLDEAEAKRKAKRRLHRKREKKGADVNENGDSSRGIGEGHDTMVTVADVFKLLQTIRASKKICSISFCPVAPKSSLATLALSLNNNLLEFHSIEADKTSKMLTIELQGHRSDVRSVTLSSDNTLLMSTSHNSVKIWNPSTGSCLRTIDSGYGLCGLIVPQNKHALIGTKDGAIEIFDVGSGTCIEVVEAHGGSIRSIVAIPNQNGFVTGSADHDIKFWEYGMKQKPGDNSKHLTVSNVRTLKMNDDVLVVAVSPDAQKIAVALLDCTVKVFFMDSLKLMHSLYGHRLPVLCLDISSDGDLIVTGSADKNLMIWGLDFGDRHKSIFAHGDSIMAVQFVGNTHYMFSVGKDRLVKYWDADKFELLLTLEGHHADIWCLAISNRGDFLVTGSHDRSIRRWDRTEEPFFIEEEKEKRLEEMFESDLDNAFGNKYVPKEEIPEEGAVALAGKKTQETLSATDSIIEALDIAEVELKRIAEHEEEKNNGKTAEFHPNYVMLGLSPSDFILRALSNVQTNDLEQTLLALPFSDALKLLSYLKDWTTYPDKVELVSRIATVLLQTHYNQLVSTPAARPLLTTLKDILHKKVKECKDTIGFNLAAMDHLKQLMALRSDALFQDAKVKLLEIRSQLSKRLEERTDPREAKRRKKKQKKSTNMHAWP 376 WD40 repeatMGGVQAEREDKDKVSLELTEEILQSMEVGMTFRDYSGRISSMDFHRASSYLVTA 75 1079 proteinSDDESIRLYDVASATCLKTINSKKYGVDLVSFTSHPMTVIYSSKNGWDESLRLLSLHDNKYLRYFKGHHDRVVSLSLCPRNECFISGSLDRTVLLWDQRAEKCQGLLRVQGRPATAYDDPGLVFAIAFGGCVRMFDARKYEKGPFEIFSVGGDVSDANVVKFSNDGRLMLLTTTDGHIHVLDSFRGTLLYTFNVKPTSSKSTLEASFSPEGMFVISGSGDGSVYAWSVRGGKEVASWLSTDTEPPVIKWAPGNLMFATGSSELSFWIPDL SKLGAYVGRK 377WD40 repeat MAAFGAAPAGNHNPNKSSEVIQPPSDSVSSLCFSPRANHLVATSWDNQVRCWEL 991148 protein TKNGASVTSVPKASMSHDQPVLCSAWKDDGTTVFSGGCDKQAKMWSLMSGGQPVTVAMHDAPIKEIAWIPEMNVLVTGSWDKTLKYWDTRQSNPVHTQQLPERCYAMTVRYPLMVVGTADRNLIVFNLQNPQAEFKRFSSPLKYQTRCVAAFPDQQGFLVGSIEGRVGVHHLDDSQISKNFTFKCHRDNNDIYSVNSLNFHPVHHTFATAGSDGTFNFWDKDSKQRLKAMSRCSQPIPCSTFNNDGTIYAYSVCYDWSKGAENHNPATAKTYIFLHLPQESEVKAKPRVGTTNRK 378 WD40 repeatMNCSISGEVPEEPVVSTKSGHVFERRLIERYVSDYGKCPVSGEPLTMDDVLPVK 232 1806 proteinMGKIVKPRPLQAASIPGLLSIFQNEWDSLMLSNFALEQQLHTARQELSHALYQHDAACRVIARLKKERDEARSLLALAERQIPMTASSDIAVNAPAMSNGRKASLDEEPGYAGKKMRPGISASIIAEITDCNLALSQQRKKRQIPSTLAPVEDLERYTQLSSYPLHKTGKPGITSLDICHSKDIIATGGIDTSAVLFDRSSGQIMSTLSGHSKKVTSVNFDAQGDMVLTGSADKTVRIWQGSEDGSYNCRHILKDHTAEVQAITVHATNNYFATASLDNTWCFYEFSTGLCLTQVEGASGSEGYTSAAFHPDGLILGTGTSNADVKIWDVKTQANVTTFSGHTGAITAISFSENGYFLATAAQDGVKLWDLRKLKNFRTFSAYDKDTGTNSVEFDHSGCYLGLAGSDIRVYQVASVKSEWNCVKTFPDLSGTGKVTCVKFGPDSKYIAVGSMDHNLRIFGLPSEDGAMES 379 WD40 repeatMAAPGVETLKKEIKELKEKIAQHRLDTDGEQPLPAAAKSKSVPEVSAALKQRRI 72 1124 proteinLKGHFGKIYALHWSADSRHLVSASQDGKLIIWNGFTTNKVHAIPLRSSWVMTCAYSPSGNLVACGGLDNLCSVYKVPHGGNKESSSAQKTYGELAQHEGYLSCCRFIKDNEIVTSSGDSTCILWDVETKTPKAIFNDHTGDVMSLAVFDDKGVFVSGSCDATAKLWDHRVHKQCVMTFQGHESDINSVQFFPDGDAFGTGSDDSSCRLFDIRAYQQINKYSSDKILCGITSVAFSKTGKSLFAGYDDYNTYVWDTLSGNQVEVLTGHENRVSCLGVSEDGKALATGSWDTLLKIWA 380 WD40 repeatMGGVEDESEPASKRMKLSSRVLRGLANGSSRTEPAAGSSLDLMARPLPIEGDEE 315 2069 proteinVIGSKGVIKRVEFVRLIAKALYSLGYEKSGARLEEESGIPLQSSVVNLFMQQISDGLWDESVVTLHKIGLSDENLVKSASFLILEQKFLELLDQEKAMDALKTLRTEITPLCIKNSRVRELSSCIISPSSCGLLNQNKRNSTRARSRSELLEELQKLLPPAVIIPERRLEHLVEQALVLQTDACMLHNSIDMEMSLYTDHQCGKEHIPCRTLQILQSHNDEVWLVQFSHNGKYLASASNDRSAIIWEVDENGSVSLKHKLTGHQKPISSVCWSPDDRQLLTCGVGETVRRWDVSSGECLRVYEKAGHGLISCAWFPDGKWICYGVSDRSICMCDLEGKEIECWKGQRTLSISDLEITSDGKQIISICRETAILLLDREAKYERMIEENQTITSFSLSKDNRYLLVNLLNQEIHLWDIKGDFRLVAKYKGLKRSRFVIRSCFGGLKQAFVASGSEDSQVYIWHKGSGELIEPLPGHSGAVNCVSWNPANHHMLASASDDRTIRIWGLNELNTRHKGARPNGVHYCNGNGTS 381 WD40 repeatMTQLAETYACMPSTERGRGILIAGNPKPGSNSVLYTNGRSVVILNLDNPLDISV 145 1968 proteinYAEHAYPATVARFSPNGEWVASADSSGAVRIWGAYNDHVLKKEFKVLSGRIDDLQWSPDGLRIVASGDGKGKSLVRAFMWDSGTNVGEFDGHSRRVLSCAFKPTRPFRIVTCGEDFLVNFYEGPPFKFKLSRRDHSNFVNCLRFSPDGNRFISVSSDKKGIIYDGKTGEKIGELSSDGGHTGSIYAVSWSPDSKQVITVSADKSAKIWDISEDGSGNLRKTLTSSGSGGVDDMLVGCLWQNNHLVTVSLGGTISIYTAGDLDKAPVSFSGHMKNVSSLSVLKGDPKVILSSSYDGLIIKWIQGIGFSGRVQRKESTQIKCLAAVDEEIVTSGYDNKVCRVSGSGDAEFIDIGCQPKDLSLALQCPEFALVSTDTGVVLLRGAKIVSTINLGFAVTASTVAPDGTEAIIGAQDGKLRIYSISGDTLTEEAVLEKHRGAISVIHYSPDLSMFASGDLNREAVVWDRASREVRLKNILYHTARINCLAWSPDSSTVATGSLDTCVIIYEVDKPASNRLTIKGAHLGGVYGLAFTDDFSVVSSG EDACIRVWKINRQ 382WD40 repeat MKVKVISRSTDEFTRERSQDLQRVFRNFDPNLRTQEKAVEYVRALNAAKLDKVF 1301488 protein ARPFVGAMDGHVDSVSCMAKNPNYLKGIFSGSMDGDIRLWDIASRRTVCQFPGHQGPVRGLAASTDGQILVSCGIDSTVRLWNVPVATLGESDGTHENLAKPLAVYVWKNAFWAVDHQWDGELFATAGAQVDIWNQNRSQPISSFEWGTDTVISVRFNPGEPNVLATSGSDRSITLYDLRMSSPTRKVIMRTKTNAISWNPMEPMNFTAANEDCNCYSYDARKLEEAKCVHKDHVSAVMDIDYSPTGREFVTGSYDRTVRIFQYNGGHSREVYHTKRMQRVFCVKFSCDASYVISGSDDTNLRLWKAKASEQLGVVLPRERRKHEYHEAVKSRYKHLPEVKRIVRHRHLPKPIYKAGILRRTVNEADRRKEERRKAHSAPGSSSAEPLRKRRIIKEIE 383 WD40 repeatMVRSIKNPKKAKRKNKGSKNGDGSSSSSSIPSMPTKVWQPGVDKLEEGEELQCD 269 1693 proteinPSAYNSLHAFHIGWPCLSFDIVRDTLGLVRTEFPHQVYFVAGTQAEKPTWNSIGIFKVSNITGKRRELVPSKPTDDADEESDSSDSDEDSDDEVGGSGTPILQLRKVGHEGCVNRIRAMNQNPHICASWGDSGHVQIWDFSSHLNALAESEADVSQGASSVFNQAPLVKFGGHKDEGYALDWSPLVPGRLVSGDCKNSIHLWEPTSGSTWNVDSTPFIGHAASVEDLQWSPTEENVFASCSVDGTIAIWDTRLGKTPAASFKAHDADVNVISWNRLATCMLASGCDDGTFSIHDLRLLKEGDSVVAHFEYHKHPVTSIEWSPHEASTLAVSSADCQLTIWDLSLEKDEEEEAEFKAKTKEQVNAPEDLPPQLLFVHQGQKDLKELHWHAQIPGMIVSTAADGFNILMPSNIQSTLPSDGA 384 CDK type AMERYKVIKELGDGTYGSVWKALNQQTHEIVAIKKMKRKYYIWEECINLREVKSL 1163 2545RKLNHPNIIKLKEVIRENNELFFIFEYMECNLYQIMKERSTPFSETAIIKFCYQILQGLSYMHRNGYFHRDLKPENLLVTSDLIKIADFGLAREVLTSPPYTDYVSTRWYRAPEVLLQSPTYTTAIDMWAVGAILAELFTLHPLFPGESELDEIYKICGVLGTPDYETWPDGMQLAAFRNFIFPQFLPVNLSVLIPHASPEAIDLITRLCSWDPQKRPTAEQALHHPFFRIGMSIPLSLGGHFQDNTCAAEVDTNFHSKKACKGRGMGEKESSLECFLGLSLGLKPSLGHLGAMGSQGVGAVKQEVGSSPGCQSNPKQSLFQVLNSRAILPLFSSSPNLNVVPVKSSLPSAYTVNSQVMWPTIAGPPAAAVTVSTLQPSILGDFKIFGKSMGLASQYAGKEASPFS 385 CDK type AMGEMGRGINNSSNNNNSNRPAWLQHYDLVGKIGEGTYGLVFLARSKLPNNRGLR 152 1582IAIKKFKQSKDGDGVSPTAIREIMLLREFSHENVVKLVNVHINHVDMSLYLAFDYAEHDLYEIIRHHREKLNHHNINQYTVKSLLWQLLNGLNYLHSNWIVHRDLKPSNILVMGEGEEHGVVKIADFGLARIYQAPLKPLSDNGVVVTIWYRAPELLLGAKHYTSAVDMWAVGCIFAELITLKPLFQGVEVKASPNPFQLDQLDKIFKVLGHPTIEKWPTLMNLPHWSKNLQQIQQHKYDNAGLHIGPIPAKSPAYDLLSKMLEYDPRKRITAAQALEHEYFRIDPQPGRNALVPSQPGEKAINYPPRLVDANTDFDGTIAPQPSQVSSGNAPSGSIASAAVPAVRPLPQQMQLMGMQRMQNPGMAAFNLGAQASMSGLNHNNIALQRGSSQQQAHQQVRRKEPNSGFPNTGYPPPPKSRRL 386 CDK type B-1MDKYEKLEKVGEGTYGKVYKARDKMTGQLVALKKTRLEMDEEGVPPSSLREISL 389 1297LQMLSQSIYVVRLLCVEHVTKKGKPLLYLVFEYLDTDLKKFIDYRRSVNAGPLPQNVIQSFMYQLLKGVAHCHSHGVLHRDLKPQNLLVDKSKGLLKVGDLGLGRAFTVPLKCYTHEVVTLWYRAPEVLLGSTHYSTPVDIWSVGCIFAEMVRRQPLFPGDCEIQQLLHIFTLLGTPTEEMWPGVKRLRDWHEYPQWKPENLARAVPNLSPTGLDLISKMLQCDPAKRISAKAAMNHPYFDDLDKSQF; 387 CDK type B-1MDGYEKMDKVGEGTYGKVYMARDKKTGQLVALKKTRLENDGEGIPPTALREISL 38 946LQMLSQDIYIVRLLDVKHTENKLGKPLLYLVFEYMESDLKKYIDSYRRSHTKMPPSMIKSFMYQLCRGVAYCHSRGVMHRDLKPHNLLVDKEKGVLKIADLGLSRAFTVPVKKYTHEIVTLWYRAPEVLLGATHYSLPVDIWSVGCIFAEMSRMQALFTGDSEVQQLMNIFRFLGTPNEEVWPGVTKLKDWHIYPEWKPQDISHAVPDLEPSGLDLLSQMLVYEPSKRISAKKALEHPYFDDLDKSQF 388 CDK type B-1MDAYEKLEKVGEGTYGKVYKAKDKNTGQLVALKKTRLESDDEGIPPTALREISL 180 1088LQMLSQDIHIVRLLDVEHTENKNGKPLLYLVFEYMDSDLKKYIDGYRRSHTKVPPNIIKSFMYQLCQGVAYCHSRGVMHRDLKPHNLLVDKQRGVVKIADLGLGRAFTIPIKKYTHEIVTLWYRAPEVLLGATHYSTPVDIWSVGCIFAEMVRLQALFIGDSEVQQLFKIFSFLGTPNEEIWPGVTKFRDWHIYPQWKPQDISSAVPDLEPSGVDLLSKMLVYEPSKRISAKKALEHPYFDDLDKSQF 389 CDK type B-1MDSYEKLEKVGEGTYGKVYKAKDKKTGKLVALKKTRLENDGEGIPPTALREISL 40 948LQMLSQDMNIVRLLDVEHTENKNGKPLLYLVFEYMDSDLKKYVDGYRRSHTKMPPKIIKSFMYQLCQGVAYCHSRGVMHRDLKPHNLLVDKQRGVLKIADLGLGRAFTVPIKKYTHEIVTLWYRAPEVLLGATHYSTPVDIWSVGCIFAEMSRMHALFCGDSEVQQLMSIFKFLGTPNEGVWPGVTKLKDWHIYPEWRPQDLSRAVPDLEPSGVDLLTKMLVYEPSKRISAKKALQHPYFDDLDKSQF 390 CDK type B-1MEKYEKLEKVGEGTYGKVYKGRDKRTGRLVALKKTPFHQEEGIPPTAIREISLL 299 1134KSLSQCIYIVKLLDVKASFNGKGKHVLFMVFEYADSDLKKHIDAHRQCNTKLSPRSIQSYMFQLCKGIAYCHSHGVLHRDLKPQNILVDQKIGLLKIADLGLGRACTVPIKSYTFEVVTLWYRAPEVLLGAKRYSMALDIWSLGCIFAELCNLQALFAGDSQIQQLINIFRLLGTPNEQLWPGVTQLSDWHEFPQWRPQDLSKVVFNLDPNGVDLLSKMLQYDPAKRISAKEALDHPYFDSLDKSQF 391 CDK type CMGCVCGKPSARAADYVESPAEKGASSNSRSSSMASRRLVAPAVMDQGIDAENGH 105 2642EGDYRTKLRGKQSNGADPVSLLSDDAEKQRHSRHHQHQQHHPIRPHHLRPQGEFVPNANSNPRFGNPPRHIEGEQVAAGWPAWLTAVAGEAIKGWIPRRADSFEKLDKIGQGTYSNVYKARDLDTGKIVALKKVRFDNLEPESVRFMAREIQVLRRLDHPNVVKLEGLVTSRMSCSLYLVFEYMDHDLAGLAACPGIKFTEPQVKCYMQQLLRGLDHCHSRGVLHRDIKGSNLLIDNGGILKIADFGLATFFHPDQRQPLTSRVVTLWYRPPELLLGATEYGVAVDLWSTGCILAELLAGKPIMPGRTEVEQLHKIFKLCGSPSEDYWKKSKLPHATIFKPQQPYKRCVAETFKDFPPSALALMEVLLAIEPADRGTATSALKSDFFTTKPLACDPSSLPKYPPSKEFDAKIRDEEARRQRAAGGRGRDAARRPSRESRAIPAPEANAELAISIQKRRLSSQGPSKSKSEKFNPQQEDGAVGFPIEPPRPMHIGIDAGATSRMYSQQFGPSHSGPLSNQISSSIWGKNQKEDEIQMAPGRPSRSSKATISDFRKPGACAPQPGADLSHLSSLVATARSNAGIDTHKDRSGMWQHNRIDAIDGVHNNGKHEFLEVPEHPNRQDWTRFQQPESFKGLDNYHLQDLPATHHRKDERVASKEATMNWQGYGGQGGDKIHYSGPLLPPSGNIDEILKEHERHIQHAVRRARQDKGRPQRSNLSQNERKAFEHRSFVSGVNGNAGYSDLVNELPISVGSNRLKVSKTRGTEEIVELRELEREPLSSVMEKYEREHEM 392 CDK type CMGCVCAKQSDILGEPESPKVKGSNLASSRWSVSSETKQLPQHSDSGILHHQHYY 187 2580HPRDESDEAKLKESNYGGSKRRTRQGRDPADLDMGIFVRTPSSQSEAELVAAGWPAWMAAFAGEAIHGWIPRRAESFEKLYKIGQGTYSNVYKARDLDNGKIVALKKVRFDSLDAESVRFMAREILVLRKLDHPNIVKLEGLVTSEVSSSLYLVFEYMEHDLAGLAACPGIKFTEPQVKCYMQQLLQGLDHCHRHGVLHRDIKGSNLLIDNGGILKIADFGLATFFYPDQKQLLTSRVVTLWYRPPELLLGATDYGVAVDIWSAGCILAELLAGKPILPGRTEVEQLHKTFKLCGSPSEDYWKESKLPHATIFKPQHPYKSCIAEAFKDFSPSALALLETLLAIEPGHRGEASGALKSEFFTTEPLSCDPSSLPKYPPSKEFDAKLRAQETRRQRDVGVRGHGSEAARRTSRLSRAGPTPNEGAELTALTQKQHSTSHATSNIGSEKPSTKKEDYTAGLHIDPPRPVNHSYETTGVSRAYDAIRGVAYSGPLSQTHVSGSTSGKKPKRDHVKGLSGQSSLQPSKPFIVSDSRSERIYEKSHVTDLSNHSRLAVGRNRDTTDPHKSLSTLMQQIQDGTLDGIDIGTHEYARAPVSSTKQKSAQLQRPSALKYVDNVQLQNTRVGSRQSDERPANKESDMVSHRQGQRIHCSGPLLHPSANIEDLLQKHEQQIQQAVRRAHHGKREALSNKSSLPGKKPVDHRAWVSSGKGNKESPYFKGKGNKELSDLKGGPTAKVTNFRQKVM 393 CDK type CMAVANPGQLNLQEAPSWGSRSVNCFEKLEQIGEGTYGQVYMAKEIETGEIVALK 220 1749KIRMDNEREGFPITAIREIKLLKKLQHENVIKLKEIVTSPGPEKDEQGKSDGNKYNGSIYMVFEYMDHDLTGLAERPGMRFSVPQIKCYMKQLLIGLHYCHINQVLHRDIKGSNLLIDNNGILKLADFGLARSFCSDQNGNLTNRVITLWYRPPELLLGSTKYGPAVDMWSVGCIFAELLYGKPILPGKNEPEQLTKIFELCGSPDESNWPGVSKLPWYSNFKPQRQMKRRVRESFKNFDRHALDLVEKMLTLDPSQRISAKDALDAEYFWTDPVPCAPSSLPRYEPSHDFQTKRKRQQQRQHDEMTKRQKISQHPPQQHVRLPPIQNAGQGHLPLRPGPNPTMHNPPPQFPVGPSHYTGGPRGAGGQNRHPQNIRPLHAAQGGGYNANRGYGGPPQQQGGGYPPHGMGNQGPRGGQFGGRGAGYSQGGPYGGPVGGRGPNVGGGNRGPQFWSEQ 394 CDK type DMQNMEDNVQSSWSLHGNKEICARYEILERVGSGTYSDVYRGRRKADGLIVALKE 438 1748VHDYQSSWREIEALQRLCGCPNVVRLYEWFWRENEDAVLVLEFLPSDLYSVIKSGKNKGENGIPEAEVKAWMIQILQGLADCHANWVIHRDLKPSNLLISADGILKLADFGQARILEEPEAIYEVEYELPQEDIVADAPGERLMEEDDSVKGVRNEGEEDSSTAVETNFGDMAETANLDLSWKNEGDMVMQGFTSGVGTRWYRAPELLYGATIYGKEIDLWSLGCILGELLILEPLFSGTSDIDQLSRLVKVLGTPTEENWPGCSNLPDYRKLCFPGDGSPVGLKNHVPSCSDSVFSILERLVCYDPAARLNAKEVLENKYFVEDPYPVLTHELRVPSPLREENNFSEDWAKWKDMEADSDLENIDEFNVVHSSDGFC IKFS 395 CDK typeD MDLNQYPEDLNPELPEGTDNVDNPDNNKGSPVPSPHPPLKPLDPSERYRKGITL 240 1631GQGTYGIVYKAFDTVTNKTVAVKKIHLGKAKEGVNVTALREIKLLKELSHPNIIQLIDAYPHKQNLHIVFEFMETDLEAVIKDRNLVFSPADIKSYLQMTLKGLAVCHKKWVLHRDMKPNNLLIAADGQLKLGDFGLARLFGSPDRKFTHQVFAVWYRAPELLFGAKQYGPAVDIWATGCIFAELLLRKPFLQGVSDLDQIGKIFAAFGTPRQSQWPDVASLPDFVEFQFVPAPSLRSLFPMASEDALDLLSKMFTLDPKNRITAQQALEHRYFSSVPAPTRPDLLPKPSKVDSSRPPKHASPDGPVVLSPSKARRVMLFPNNLAGILPKQVSQSTTGGTPIEFDMPTQKLREVCPRSRITESGKKHLKRKTMDMSAALDECAREQEGQEGKTILDPDHQRSAKKEKHM 396 Cyclin AMAGGQENCVRITRARAACVSKASAPVIQSQVDEKKSRKRAPKRAAVDDLAANAS 252 1604GSQPKRRAVLGDVTNLHAAATDCLSTAEDQVDAPNPSIKGRARNKKKEARTSTKVVKDEIHPESNPLADHSSNLSECQKPPAAKLAEQRSLRGVPSKAKQGGSSNSQSCSKHTDIDKDHTDPQMCTTYVEDIYEYLRNAELKNRPSANFMETAQNDITPNMRAILVDWLVEVSEEYKLVPDTLYLTVSYIDRYLSANPTSRHKLQLLGVSCMLIASKYEEVCPPHVEEFCYITDNTYTRDEMLSMERKILIFLNFEMTKPTTKSFLRRFVRASQAGNKAPSLHMEFLANYLAELTLMECSFLQYLPSLIAASTVFLSRLTLDFLTNPWNPTLAHYTGYKASQLKDCVMAIYNVQMNRKGSTLVAIREKYQQHKFKCVASLPPPPFIAERFFEDTPN 397 Cyclin AMTGTQASNVRITRARAAKSTLNNALPPLPPAQGKPRGKRAATESNISGFSVAAE 261 1817PLKRRAVLSDVSNICKEAAAVDCLKKPKAVKVVSQNANAKGRGRGIPRNNKKITQEAEIKKETSPAICNVDDASAGNAIGDDKQNNNVNPLKEVQDNPKELNPIAEQISVHPHCKQSVEKPNEKEIVVSDNKAAIASLKQQSTLQSLRIPKQPKYSLKQGNPVPLANLHEDVGRSSCSDFIDIDSEYKDPQMCTAYVTDIYANMRVVELKRRPLPNFMETTQRDINANMRSVLIDWLVEVSEEYKLVPDTLYLTVSYIDRFLSANVVNRQRLQLLGVSCMLVASKYEEICAPPVEEFCYITDNTYKKEEVLEMEISVLNRLQYDLTTPTTKTFLRRFIRAAQASCKVSSLHLEFMGNYLAELTLVEYDFLKYLPSLIAAAAVFVARMTLDPMVHPWNSTLQHYTGYKVSDMRDCICAIHDLQLNRKGCTLAAIREKYNQPKFKCVANLFPPPIISPQFLIDNEV 398 Cyclin BMAAPNQNALLINNNNRRPLVDIGNLVGALNAQCNISKNGARKRAFGDIGNLVED 167 1576LDAKCTISKYWVRKRPRTNFGVNANKGASSSTQGQGIVVRGEQKAWDRIVWGNKQSCAIKMNAQHVTATQRGTAISISDIIDSSVQDGGIKAPSQLKARKQTVRTVTATLTARSEDSLRDVLEVPPGIDDGDRDNPLAVVEYVEDIYHFYRKIEVRSCVPPDYMTRQLEIKDSMRGVIIDWLIEVHRTFLLMPETLYLTVNIIDRYLSIQSVTRNELQLMGITAMFIASKYEEISPPKINDLVYITKDAYTSKQIVNMEHTILNRLKFKLTVPTPYVFLVRFLKAAGPDKVMKNLAFFLVDLCLLHYKMIKYSPSMLAAAAVYTAQCTLKKHPYWNKTLILHIGYSEAHLRECAHLMADLHLKAEGSNLKSVYKKYSYPIFGSVAFLSPAKIPAGTVAAPAIDKCAHQIYLRNLR 399 Cyclin BMFPNKQTQGLVQNKKMASKAAQPKAMVPPQRVPPAANNRRALGDIGNIVADVGG 183 1598KCNVTKDGVNGKPLAQVSRPITRSFGAQLLAQAAANKGISAANNQTQVPVVIPKADVRGNKQRRTSKSKDIPPTTVVTNESDDCVIIEQAQRIKPTCNHNVGAVGNKEKPQLLTAKPKSLTASLTSRSAVALRGFRFDDEMTEAEEDPLPNIDVGDRDNQLAVVEYVEDIYKFYRRTEQMSCVPDYMPRQQEINPKMRAVLINWLIEVHYRFGLMPETLYLTTNLIDRYLATQLVSRSNYQLVGATAMLLASKYEEIWAPEMNDFLDILENKFERKHVLVMEKAMLNKLKFHLTVPTPYVFLVRFLKAAASDEEMENLVFFLMELSLMQYVMIKFPPSMLAAAAVYTAQITLKKTTVWNDVLKRHTGYSEIDLKECTRLMVAFHQSSEESKLNVVFKKYSMPEYDSVALIKPAKLPA 400 Cyclin DMAPSFDCVANAYIESCEDQEKLRQNAQILAQSGENDVDEPVSMLVQRETHYMLP 98 1126EDYLQRLRNRTLDVNVRREAVGWILKVHSFYNFGAPTAYLAVNYLDRFLSRHRMPQGVKAWMIQLMAVACLSLAAKMEETQVPLPSDLQREDARFIFDARTIQRMELLILSTLQWGMRSITPFSFIDYFAYRAVQGHGHGHDATPKAVMSRAIELILSTTEEIDFMEYRPSAIAAAALLCAAEEVVPLQAVHYKRALSSSITDVDKDKMFGCYNLIQETIIEGGCYWTPMSLQSTEKTPVGVLDAAACLSNTPTSSYSVKPYASVTAAKRRKLNEICSALLVSQAHPC 401 Cyclin DMAANFWTSSHCKELLDAEKVGIVHPLDKDQGLTQEDVKIIKINMSNCIRTLAQY 148 894VKLRQRVVATAITYCRRVYTRKSFTEYDPQLVAPTCLYLASKAEESTVQAKLVIFYMKKYSKHRYEIKDMLEMEMKLLEALDYYLVIYHPYRPLIQFLQDAGLNDLKVTAWALVNDTYRTDLILTYPPYMIALACIYFACIMEEKDAQAWFEELRVDMNEIKNISMEIVDYYDNYRVIPDEKMNSALNKLPHRF 402 Cyclin DMAPALSSSYECLSHLLCAEDASNVVGCWDEDESKIFCEEEEGFGIQHFPDFPVP 287 1363DDDEIRVLVRKESQYMPGKSYVQSYQNLGLDFTARQNAIGWILKVHGSYNFGPLTAYLSINYLDRFLSRNPLPKAKVWMLQLLSVACLSLAAKMEETQVPLLLDLQAEEPDFLFEPRTIQRMELLVLSTLEWRMLSVTPFSFVDYFLQGGGGRKPPPRAMVARANELIFNTHTVLDFLEHRPSAIAAAAVICAAEEVLPLEAAQYKETILSCSLVDKEWVFGSYNLIQEVLIEKFSTPKKAKSASSSIPQSPVGVLDAFCLSNNSNNTSLEASLSVNLYASVAAKRRKLNDYCNTWRMFQHSTC 403 Cyclin DMAPNCIDCAPSDLFCAEDAFGVVEWGDAETGSLYGDEDQLHYNLDICDQHDEHL 251 1348WDDGELVAFAEKETLYVPNPVEKNSAEAKARQDAVDWILKVHAHYGFGPVTAVLSINYLDRFLSANQLQQDKPWMTQLAAVACLSLAAKMDETEVPLLLDFQVEEAKYIFESRTIQRMELLVLSTLEWRMSPVTPLSYIDHASRMIGLENHHCWIFTMRCKEILLNTLRDAKFLGLLPSVVAAAIMLHVIKETELVNPCEYENRLLSAMKVNKDMCERCIGLLIAPESSSLGSFSLGLKRKSSTINIPVPGSPDGVLDATFSCSSSSCGSGQSTPGSYDSNNSSILCISPAVIKKRKLNYEFCSDLHCLED 404 Cyclin-MPQIQYSEKYTDDTYEYRHVVLPPETAKLLPKNRLLNENEWRAIGVQQSRGWVH 229 510 dependentYAIHRPEPHIMLFRRPLNYQQNQQQQAGAQSQPMGLKAQ kinase regulatory subunit 405Cyclin- MDQIEYSEKYYDDTYEYRHVELPPDVARLLPKNRLLTENEWRGIGVQQSRGWVH 92 409dependent YAIHCSEPHIMLFRRPLNYEQNHQHPEPHIMLFRRPLNCQPNHQPQAHHPT kinaseregulatory subunit 406 Cyclin-MDQIEYSEKYYDDTYEYRHVELPPDVARLLPKNRLLTENEWRGIGVQQSRGWVH 64 381 dependentYAIHCSEPHIMLFRRPLNYEQNHQHPEPHIMLFRRPLNCQPNHQPQAHHPT kinase regulatorysubunit 407 Cyclin-MPQIQYSEKYYDDTYEYRHVVLPPDVARLLPKNRLLNENEWRGIGVQQSRGWVH 68 349 dependentYAIHRPEPHIMLFRRHLNYQQNQQQQAQQQPAQAMGLQA kinase regulatory subunit 408Histone MALVETEPVTLIHPEEPKKFKKKPTPGRGGVISHGLTEEEARVKAIAEIVGAMV 125 1849acetyltransferase EGCRKGEDVDLNALKAAACRRYGLSRAPKLVEMIAALPDGERAAVLPKLKAKPVRTASGIAVVAVMSKPHRCPHIATTGNICVYCPGGPDSDFEYSTQSYTGYEPTSMRAIRARYNPYVQTRSRIDQLKRLGHTVDKVEFILMGGTFMSLPADYRDYFIRNLHDALSGHTSSNVEEAVCYSEHSATKCTGLTIETRPDYCLGPHLRQMLSYGCTRLEIGVQSTYEDVARDTNRGHTVAAVADCFCLAKDAGFKVVAHMMPDLPNVGVERDMESFREFFENPAFRADGLKIYPTLVIRGTGLYELWKTGRYRNYPPEQLVDIIARVLALVPPWTRVYRVQRDIPMPLVTSGVEKGNLRELALARMDDLGLKCRDVRTREAGIQDIHHKIRPEVVELVRRDYCANEGWETFLSYEDTRQDILVGLLRLRKCGHNTTCPELKGRCSIVRELHVYGTAVPVHGRDADKLQHQGYGTLLMEQAERIAWKEHRSIKIAVISGVGTRHYYRKLGYELEGPYMMKYLN 409 HistoneMLGFRDLYTSICEHLQRASGRLPIIAAATSLISTPEIAAVEKENKAPNSVDKMG 70 1602acetyltransferase MGSADESGRFSTSNGQFMNMNNGVVKEEWKGGVPVVPSAPTTVPVITNVKLETPSSPDHDMARKRKLGFLPLEVGTRVLCKWRDGKFHPVKIIERRKLPNGATNDYEYYVHYTEFNRRLDEWVKLEQLELDSVETDADEKVDDKAGSLKMTRHQKRKIDETHVEGNEELDAASLREHEEFTKVKNITKIELGRYEIETWYFSPFPSEYNNCEKLYFCEFCLNFMKRKEQLQRHMRKCDLKHPPGDEIYRSGTLSMFEVDGKKNKVYAQNLCYLAKLFLDHKTLYYDVDLFLFYILCECDERGCHMVGYFSKEKHSEESYNLACILTLPPYQRKGYGKFLISFSYELSKKEGKVGTPERPLSDLGLLSYRGYWTRVLLDILKKHKSNISIKELSDMTAIKADDVLSTLQGLDLIQYRKGQHAICADPKVLDRHLKAVGRGGLEVDVCKLIWTPYKEQ 410 HistoneMGSLDESTCSEEIRDEGKDSIRTKFKVESTVNNAQNGGNDNSKKKRAAGLPLEV 140 1465acetyltransferase GIRLLCKWRDSKLHPVKIIERRKLPNGFPQDYEYYVHYTEFNRRLDEWVKLEQFELDSVETDADEKIEDKGGSLKMTRHQKRKIDEIHVEEGQGHEDFDPASLREHEEFTKVKNIAKVELGRYEIETWYFSPFPPEYSHCEKLFFCEFCLNFMKRKEQLQRHMRKCDLKHPPGDEIYRNGTLSMFEVDGKKNKIYGQNLCYLAKLFLDHKTLYYDVDLFLFYVLCECDDRGCHVVGYFSKEKHSDEAYNLACILTLPPYQRKGYGKFLIAFSYELSKKEGKVGTPERPLSDLGLLSYRGYWTRILLDILKKQRGNISIKELSDMTAIKVEDVISTLQVLDLIQYRKGQHVICADPKVLDRHLKAAGIAGLEVDVSKLI WTPYKEQCG 411Histone MASAPMVGCDDSRDKHRWVESKVYMRKGHGKGSKGNAGFNAQNSTAQVRRENDN 628 2565acetyltransferase MGNSIADNGKSEAASEGLSSLSRKQITVNQDHPPNETSSMPAVGGLQNIDTHVTFKLEGCSKQEIWELRKKLTNELEQVRGTFKKLEARELQLRGYSVSAGVNTSYSASQFSGNDMRNNGGKEVTSEVASGGAITPKQAQRESNPPRQLSISLMENNQAASDMGEKGKRTPKANQYYRNSEFVLGKDKFPPAESKKSKSTGNKKISQSKVFSKETMQVGKEFMPQKSVNEVFKQCSLLLTKLMKHKYGWVFNLPVDAQALGLHDYHTIIKRPMDLGTVKSKLEKNLYNSPASFAEDVKLTFSNAMTYNPKGHEVHTMAEQLLQLFEERWKTIYEEHLDGKMRFGSGQGLGASSSTKKLPFQDSKKNIKKSEPAGGPSPPKPKSTNHHASRTPSAKKPKAKDPHKRDMTYEEKQKLSTNLQNLPQERLELIVQIIKKRNPSLCQHDEEIEVDIDSFDTETLWELDRFVTNYKKSLSKNKKKALLADQAKRASEHGSARNKHPMIGRELPMNNKKGEQGEKVVEIDHMPPVNPPVVEVEKDGVYAKRSSSSSSSSSDSGSSSSDSDSGSSSGSESDAYAATSPPAGSNTSARG 412 HistoneMEGHSGALGFGQGFSRSSQSPNLSPSPSHSASASVTSSGQKRKRNEVEHAGVAS 55 1818acetyltransferase NSTGMFAVPPSHIYSHLHPMSMSMPMPMHNSHPSSLSESRDGALTSNDDDDNLTGGNQSQLDSMSAGNTDGREDFDDEDDDDDDEEDDDEVEGDEEDQDHDPDADDDSDDGHDSMRTFTAARLDNGAPNSRNLKPKADAAGVAIAPTVKTEPILDTVKEEKVSGNNNNNSVSANNAQVAPSGSAVLLSAVKEEANKPTSTDHIQTSGAYCAREESLKREEDADRLKFVCFGNDGIDQHMIWLIGLKNIFARQLPNMPKEYIVRLVMDRSHKSVMIIKQNQVVGGITYRPYLSQKFGEIAFCAITADEQVKGYGTRLMNHLKQHARDVDGLTHFLTYADNNAVGYFIKQDFTKEIKLEKERWHGYIKDYDGGILMECKIDPKLPYTDLPAMIRWQRQTIDEKIRELSNCHIVYSGIDIQKKEAGIPRKPIKVEDIPGLKEAGWTTDQWGHSRFRLLNSPSEGLPNRQVLHAFMRSLHKAMVEHADAWPFKEPVDPRDVPDYYDIIKDPMDVKRMFTNARTYNTHETIYYKCANR 413 HistoneMEESGNSLTSGPDGSKRRVSYFYDSDIGNYYYSQGHPMKPHRIRMAHSLIVHYA 259 1710deacetylase LDEKMEVCRPNLLQSRELRVFHADDYISFLQSVTPETQHEQLRQLKRFNVGEDCPVFDGLYNFCQTYAGGSVGAAIKLNNKEADIAINWSGGLHHAKKCEASGFCYVNDIVLAILELLKVHQRVLYIDIDIHHGDGVEEAFYSTDRVMSVSFHKFGDYFPGTGHLKDVGYGKGKYYSLNVPLNDGIDDESYKNLFRPIIQKVMEIYQPEAVVLQCGADSLSGDRLGCFNLSVKGHADCVRFLRSFNVPLVLVGGGGYTIRNVARCWCYETAVAVGVEPQDKLPYNEYYEYFGPDYTLHVAPSNMENQNSAKELAKIRNTLLEQLKRIQHVPSVPFQERPPDTKFPEEDEEDYEKRPKGHKWGGEYFGSESDEEQKPQNRDIDISDKPGIRRQSPPNVEAAKKIKVEEEDGDIGIVNENDGAKWPLGEAG 414 HistoneMEESGNSLTSGPDGSKRRVSYFYDSDIGNYYYSQGHPMKPHRIRMAHSLIVHYA 356 1807deacetylase LDEKMEVCRPNLLQSRELRVFHADDYISFLQSVTPETQHEQLRQLKRFNVGEDCPVFDGLYNFCQTYAGGSVGAAIKLNNKEADIAINWSGGLHHAKKCEASGFCYVNDIVLAILELLKVHQRVLYIDIDIHHGDGVEEAFYSTDRVMSVSFHKFGDYFPGTGHLKDVGYGKGKYYSLNVPLNDGIDDESYKNLFRPIIQKVMEIYQPEAVVLQCGADSLSGDRLGCFNLSVKGHADCVRFLRSFNVPLVLVGGGGYTIRNVARCWCYETAVAVGVEPQDKLPYNEYYEYFGPDYTLHVAPSNMENQNSAKELAKIRNTLLEQLKRIQHVPSVPFQERPPDTKFPEEDEEDYEKRPKGHKWGGEYFGSESDEEQKPQNRDIDISDKPGIRRQSPPNVEAAKKIKVEEEDGDIGIVNENDGAKWPLGEAG 415 HistoneMEFWGVEVKPGEALTCDPGDERYLHMSQAAIGDKEGAKENERVSLYVHVDGKKF 261 1298deacetylase VLGTLSRGKCDQIGLDLVFEKEFKLSHTSQTGSVFVSGYTTVDHEALDGFPDDEDLESSEDEEEELAQITTLTAKENGGKTGAKPVKPESKSSVTDKAAAKGKPEVKPPVKKQEDDSDSDEDEDEDEDEDEDDDDEDDEDMKDASASDDGDEEDDSDEESDDDEEEDEETPKPAAGKKRPMPASDNKSPATDKKAKITTPAGGQKPGADKGKKTEHIATPYPKHGAKGPASGVKGKETPLGSKQTPGSKVKNSSTPESGKKSGQFKCQSCSRDFATEGALSSHNAAKHGGK 416 HistoneMMETGGNSLPSGPDGVKRKVAYFYDPEVGNYYYGQGHPMKPHRIRMTHALLVQY 365 2251deacetylase GLHKEMQILKPYPARDRDLCRFHADDYVAFLRGITPETIQDQVKALKRFNVGDDCPVFDGLYQYCQTYAGGSVGGAVKLNHKLCDIAINWAGGLHHAKKCEASGFCYVNDIVLAILELLKYHKRVLYVDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGDIRDIGCGKGKYYAVNVPLDDGIDDESFQSLFKPIIQQVMLVYNPEAIVLQCGADSLSGDRLGCFNLSVKGHAECVRYMRSFNVPLLMVGGGGYTVRNVARCWCYETGVAVGVEIDDKMPQHEYYEYFGPDYTVHVAPSNMENKNTKQYLDKIRSKILENINSLPCAPSAQFQVQPPDTDFPELEEEDYDERTRSHKWDGASCDSDSENGDLKHRNHDVEESAFPRHNLANISYNTKIKLEGVGTGGLDMAAGTDTKKNDESFEAMDYESGEELRQDHFASTINASQPCDPALLTGVQNQLQSTDTVKPIEQSGNAPGIPPPSVATVSTGTRPSSISRTSSLNSMSSVKQGSILGPNPPQGLNASGLQFPVPTSNSPIRQGGSYSITVQAPDKQGLQNHMKGPQNMPGNS 417 HistoneMPPKDRVAYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVLSYELHKKMEIYRPHK 156 1454deacetylase AYPVELAQFHSADYVEFLHRITPDTQHLFTKELVKYNMGEDCPVFENLFEFCQIYAGGTIDAAHRLNNQICDIAINWSGGLHHAKKCEASGFCYINDLVLGILELLKHHARVLYVDIDVHHGDGVEEAFYFTDRVMTVSFHKYGDMFFPGTGDVKEVGEREGKYYAINVPLKDGIDDASFTRLFKTIITKVVDIYQPGAIVLQCGADSLAGDRLGCFNLSIDGHAQCVRIVKKFNLPLLVTGGGGYTKENVARCWSVETGVLLDTELPNEIPDNDYIKYFAPDYSLKINTAGNMENLNSKTYLSAIKVQVMENLRAIQHAPSVQMHEVPPDFYIPDIDEDELNPDERMDQHTQDRQIQRDDEYYDGDNDIDHDMEEAS 418 HistoneMDSSKSEEANILHVFWHEGMLNHDLGTGVFDTLEDPGFLEVLEKHPENADRVRN 203 1348deacetylase MLSILRKGPIAPYTEWHTGRAAYLSELYSFHRPDYVDMLAKTSTAGGKTLCHGTRLNPGSWEAALLAAGTTLEAMRYILDGHGKLSYALVRPPGHHAQPTQADGYCFLNNAGLAVELAVASGCKRVAVVDIDVHYGNGTAEGFYERDDVLTISLHMNHGSWGPSHPQTGFHDEVGRGKGLGFNLNVPLPNGTGDKGYEHAMHELVVPAISKFMPEMIVLVIGQDSSAFDPNGRECLTMEGYRKIGQIMRQQADQFSGGRLVVVQEGGYHITYAAYCLHATLEGVLCLPHPLLSDPIAYYPEHDIYSERVTFIKNYWQGIISTTD KRN 419 HistoneMEESGNALVSGPDGSKRRVTYFYDADIGNYYYGQGHPMKPHRMRMAHNLIVHYG 229 1644deacetylase LHQRMEVCRPHLAQSKDIRAFHTDDYIHFLSSVAPDTQQEQLRQLKRFNVGEDCPVFDGLFNFCQSSAGGSIGAALKLNRKDADIAINWAGGLHHAKKCEASGFCYVNDIVLGILELLKVHQRVLYIDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGHIKDVGYGKGKYYALNVPLNDGIDDESYKHLFRPIIQKVMEVYQPEAVVLQCGADSLSGDRLGCFNLSVKGHADCVRFVRSFNIPLMLVGGGGYTIRNVARCWCYETAVAVGVEPQDKLPYNEYYEYFGPDYTLYVAPSNMENLNTEKDLEKMRNVLLEQLSKIQHTPSVPFQERPPDTEFNDEEEEDMEKRSKCRIWDGEYVGSEPEEDGKLPRFDADTYERSVLKHENKRLVPVSNVEPLKRIKQEEDGAAV 420 HistoneMPPKDRVAYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVLSYELHKKMEIYRPHK 156 1454deacetylase AYPVELAQFHSADYVEFLHRITPDTQHLFTKELVKYNMGEDCPVFENLFEFCQIYAGGTIDAAHRLNNQICDIAINWSGGLHHAKKCEASGFCYINDLVLGILELLKHHARVLYVDIDVHHGDGVEEAFYFTDRVMTVSFHKYGDMFFPGTGDVKEVGEREGKYYAINVPLKDGIDDASFTRLFKTIITKVVDIYQPGAIVLQCGADSLAGDRLGCFNLSIDGHAQCVRIVKKFNLPLLVTGGGGYTKENVARCWSVETGVLLDTELPNEIPDNDYIKYFAPDYSLKINTAGNMENLNSKTYLSAIKVQVMENLRAIQHAPSVQMHEVPPDFYIPDIDEDELNPDERMDQHTQDRQIQRDDEYYDGDNDIDHDMEEAS 421 HistoneMDLNLVSHGEEEEGVRRRKVGIVYDERMCKHATPEDQPHPEQPDRIRVIWDKLN 27 2222deacetylase SAGVLHKCVMVEAKEASEEQLAGVHSRKHIEVMKSIGTARYNKKKRDKLAASYSSIYFSQGSSEAALLAAGSVVEISEKVASGELDAGVAIVRPPGHHAEADKAMGFCLFNNIAIAAKHLVHERPELGVQEVLIVDWDVHHGNGTQHMFWTDPHVLYFSVHRFDAGTFYPGGDDGFYDKIGEGKGAGYNINVPWEQGKCGDADYLAVWDHVLVPVAKSYDPDMVLISGGFDAALGDPLGGCRLTPYGYSLMTKKLMEFAGGKIVLALEGGYNLKSLADSFLACVEALLKDGPSRSSVLTHPFGSTWRVIQAVRKELSSFWPALNEELQLPRLLKDASESFDKLSSSSSDESSASEDEKKIAEVTSIMEVSPDPSSILALTAEDIAQPLAGLKIEEAGTDSQRSSDHTLLDLTNDDTQKLKQFEGEIFVMIGDEESVPSASSSKDQNESTVVLSKSNIKAHSWRLTFSSIYVWYASYGSNMWNPRFLCYIEGGQVEGMAKRCCGSEDKTPPQRIQWKVVPHRMFFGRSYTNTWGSGGVSFLDPNCSDTSEAHVCLYKITLAQFNDLLLQENNLNCGTEHPLVDLSSIDAIRNGNSILELIKDSWYGTLIYLGMEGGLPIVTFTCSVCDVEKFKHGQLPLCPPSSRYENILIRGLVQGKKLSEDDATAYIRAASTSPLL 422 PeptidylprolylMADEDLDLSDVGEVEDEPGEEIESTPPLAVGQEKEINSLALKKKLLKVGTRWET 71 1759 isomerasePENGDEVTVHYTGTLPDGTKFDSSRDRGEPFTFKLGQGQVIKGWDQGIVTMKKGERALFTIPPELAYGSSGVRPTIPPNATLQFDVELLSWTNIVDVCNDGGILKRIISEGEKYERPKDPDEVTVKYEAKLEDGTLVAKSPEEGVEFYVNDGHFCPAIAKAVKTMKRGESVILTIKPTYAFGERGKDAEEGFAAIPPNATLTTSLELVSFKAVIAVTEDKKVIKKILKEADGYDKPSDGTVVQIRYTAKLQDGTIFEKKGYEGEEPFQFVVDEEQVIAGLDKAVETMKTGEIALITIGAEYGFGNFETQRDLAVIPPNSTLIYEVEMISFTKEKESWDMDTTEKIEASKQKKEQGNSLFKVGKYQRAAKKYEKAAKYIEHDSSFSAEEKKQSKVLKVSCNLNHAACRLKLKDFKEAVKLCSKVLELESQNVKALYRRAQAYIETADLDLAEFDIKKALEIEPQNREVQLEYKILKQKQIEYNKKDAKLYGNMFAKLNKLEAFEGKVLS 423 PeptidylprolylMADEGLELSDVAEVEDEPGEEFESAPPLVVGQEKELNSSGLKKKLLKAGTRCET 358 2040isomerase PENGDEVTVHYTGTLLDGTKFDSSRDRGEPFTFNIGQGQVIKGWDQGIVTMKKREHALFTIPPELAYGASGMPPTIPPNATLQFDVELLSWTNIVDVCKDGGILKRIISDGEKYERPKDPDEVTVKYEAKLEDGMLVAKSPEEGVEFYVNDGNFCPAIVKAVKTMKKGENVTLTIKPAYAFGEQGKDAEEGFAAIPPNATITINLQLVSFKAVKEVTEDKKVIKKILKEADGYDKPSDGTVVQIRYTAKLQDGTIFEKKGYAGEEPFQFVVDEEQVIAGLDKAVETMKTGEVALITIGPEYGFGNIETQRDLAVIPPYSTLIYEVEMVSFTKEKESWDMNTTENIEASKQKKEQGNSLFKVGKYLRAAKKYDKAAKYIEHDNSFSAEEKKQSKVLKVSCNLNHAACCLKLKDFKKAVKLCSKVLELESQNVKALYRRAQAYIETADLDLAEFDIKKALEIEPQNREVRLEYLILKQKQIEYNKKDAKLYGNMFARQNKLEAIEGKD 424 PeptidylprolylMPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGTGRSGKPLH 238 756 isomeraseFKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP VVIADSGQLA 425Peptidylprolyl MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGNGRSGKPLH238 756 isomerase FKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP VVIADSGQLA 426Peptidylprolyl MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGTGRSGKPLH238 756 isomerase FKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP VVIADSGQLA 427Peptidylprolyl MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGTGRSGKPLH238 756 isomerase FKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP VVIADSGQLA 428Peptidylprolyl MADDFELPESAGMMENEDFGDTVFKVGEEKEIGKQGLKKLLVKEGGSWETPETG176 1912 isomeraseDEVEVHYTGTLLDGTKFDSSRDRGTPFKFKLGQGQVIKGWDQGIATMKKGENAVFTIPPDLAYGESGSQPTIPPNATLKFDVELLSWASVKDICKDGGIFKKIIKEGEKWEHPKEADEVLVKYEARLEDGTVVSKSEEGVEFYVKDGYFCPAFAIAVKTMKKGEKVLLTVKPQYGFGHQGREAIGNDVARSTNATLLVDLELVSWKVVDEVTDDKKVLKKILKQGEGYERPNDGAVVKVKYTGKLEDGTIFEEKGSDEEPFEFMAGEEQVVDGLDRAVMTMKKGEVALVSVAAEYGYQTEIKTDLAVVPPKSTLIYEVELVSFVKEKESWDMNTAEKIEAAGKKKEEGNALFKVGKYFRASKKYEKATKYIEYDTSFSEEEKKQSKPLKVTCNLNNAACKLKLKDYTQAEKLCTKVLEVESQNVKALYRRAQAYIQTADLELAELDIKKALEIDPNNRDVKLEYRALKEKQKEYNKKEAKFYGNMFARMSKLEELESRKSGSQKVETANKEEGSDAMAVDGESA 429 PeptidylprolylMAASLTPLGAGLAYATIYDQAKVRKLEPTKRSLIALCQHSDSQHRRFITRKYHV 64 765 isomeraseNVQILNRRDAIRLIGLAAGLCIDLSLMYDARGAGLPPQENAKLCDTTCEKELENAPMITTESGLQYKDIKIGNGPSPPIGFQVAANYVAMVPSGQVFDSSLDKGQPYIFRVGSGQVIKGLDEGLLSMKVGGKRRLYIPGPLAFPKGLNSAPGRPRVAPSSPV IFDVSLEFIPGLESEEE430 PeptidylprolylMSAASLSADMAIRGTILGKTALHVLGPQVVSQCRQPVMFKCPPHTLRKMRFSAQ 93 881 isomeraseDLQSKNFYSGFTPFKSVFISTSKRSWQAGSARAMSQDAAFQSKVTTKCFLDIEIGGDPAGRIVLGLFGEDVPKTAENFRALCTGEKGFGYKGSSFHRIIKDFMLQGGDFDRGDGTGGKSIYGRTFEDENFKLAHVGPGVLSMANAGPNTNGSQFFICTVKTPWLDKRHVVFGQVIEGMEIVKKLESEETNRTDRPKRPCRIVDCGELP 431 PeptidylprolylMGRIKPQTLLQQSKKKKVPGRISVSTIIVCNLIIIFLMFSLVGIYRQRAKRNRA 372 1070isomerase TSRSDGDEEMENFGRSKINSVPHQAIVNTTKGLITLELFGKSSAHTVEKFVEWSERGYFNGLPFYRVIKHFVIQVGDPKFAGNREDWTVGGQLNVQLEFSPKHEAFMLGTSKLEDQGDGFELFITTAPIPDLNDKLNVFGRVIKGQDVVQEIEEVDTDEHFQ PKSPIIINDVRLKDEL432 PeptidylprolylMARQSTLLLFWSLVFLGAIVFTQAKHEELEEVTHKVYFDVDIAGKPAGRVVIGL 28 594 isomeraseFGKAVPKTVENFRALCTGEKGVGKSGKPLHYKGSFFHRIIPSFMIQGGDFTLGDGRGGESIYGTKFADENFKLKHTGPVFITTVTTDWLDGRHVVFGKIISGMDVVYKVEAEGRQSGQPKRKVKIADSGELSMD 433 PeptidylprolylMARQSTLLLFWSLVFLGAIVFTQAKHEELEEVTHKVYFDVDIAGKPAGRVVIGL 34 648 isomeraseFGKAVPKTVENFRALCTGEKGVGKSGKPLHYKGSFFHRIIPSFMIQGGDFTLGDGRGGESIYGTKFADENFKLKHTGPGFLSMANAGPDTNGSQFFITTVTTDWLDGRHVVFGKIISGMDVVYKVEAEGRQSGQPKRKVKIADSGELSMD 434 PeptidylprolylMEMDEIQEQSQPQSSEKQDISQESDTGNDKTINAEKITSENAEVEEDDMLPPKV 481 1611isomerase NTEVEVLHDKVTKQIIKEGSGNKPSRNSTCFLHYRAWAESTMHKFQDTWQEQQPLELVLGREKKELSGFAIGVAGMKAGERALLHVDWQLGYGEEGNFSFPNVPPRANLIYEAELIGFEEAKEGKARSDMTVEERIEAADRRRQQGNELFKEDKLAEAMQQYEMALAYMGDDFMFQLFGKYKDMANAVKNPCHLNMAQCLLKLNRYEEAIGQCNMVLAEDEKNIKALFRRGKARATLGQTDDAREDFQKVRKFSPEDKAVIRELRLLAEHDKQVYQKQKEMFKGLFGQKPEQKPKKLHWFVVFWQWLLSMIRTIFRMRSKTD 435 PeptidylprolylMAGAGEGTPEVTLETSMGPITVELYHKHAPKTCRNFLELSRRGYYNNVKFHRVI 93 584 isomeraseKDFMVQGGDPTGTGRGGESIYGPRFEDEITRDLKHTGAGILSMANAGPNTNGSQFFISLAPTPWLDEKHTIFGRVCKGMDVVKRLGNVQTDKNDRPIHDVKILRTTVKD 436Peptidylprolyl MMDPELMRLAQEQMSKISPDELMKMQRQIMANPDLMRMASENMKNLKPEDIRFA250 1869 isomeraseAEQMKNVRKEEMAEISERISRASPEEIEAMKARANLQSAYQLQVAQNLKDQGNQLHARMKYSEAAEKYLQARNNLTGIPFSEAKSLLLASSSNLMSCYLKTGQYEECVQTGSEVLAYDAMNVKALYRRGQAYKQIGKLELAVADLRKAVEVSPEDETIAQALREASTELMEKGGTQDQNGPRIEEIIEEEAVQPTAEKYPQSAPMVTSVTEDVSDDEQGSEDQNGFSRDSFQATNAPDGQMYAESLRNLTENPDMLRTMQSLMKNVDPDSLVALSGGKLSPDMVKTVSGMFGRMSPEEIQNMMKMSSTLSRQNPSTSSRFDDITRGHSNMDSSPQSVSVDNDLFEENQNRVGESSTNLSSSAAFSGMPNFSAEMQEQVRNQMNDPATRQMFTSMIQNMSPEMMASMSEQFGVKLSPEDAVKAQNAMASLSPNDLDRLMNWATRLQTAIDYARKIKNWILGRPGLIFAISMLLLAIILHRFGYIGD 437 PeptidylprolylMGVEKEILRPGNGPKPRPGQSVTVHCTGYGKNEDLSQKFWSTKDPGQKPFTFTI 84 422 isomeraseGQGRVIKGWDEGVLDMQLGEIFKLRCSPDYGYGSNGFPAWGIRPNSVLVFEIEV LSVN 438Peptidylprolyl MPNPRCYLDITIGEELEGRILVELYSDVVPKTAENFRALCTGEKGIGPHTGVPL128 1213 isomeraseHYKGLPFHRVIKGFMIQGGDISAQNGTGGESIYGLKFDDENFQLKHERRGMLSMANSGPNTNGSQFFITTTRTSHLDGKHVVFGKVIKGMGVVRGIEHTPTESNDRPSLDVVISDCGEIPEGSDDGIANFFKDGDLYPDWPADLDEKSAEISWWMNAVDSAKCFGNENYKKGDYKMALRKYRKALRYLDICWEKEEIDEEKSNHLRKTKSQIFTNSSACKLKLGDLKGALLDTEFAMRDGEDNVKALFRQGQAYMALKDVDSAVASFKKALQLEPNDAGIRKELAVATKMINDRRDQERRAYARMFQ 439 PeptidylprolylMGDVIDLNGDGGVLKTIIRSAKPGAMQPTEDLPNVDVHYEGTLADTGEVFDTTR 265 837 isomeraseEDNTLFSFELGKGTVIKAWDIAVKTMKVGEVARITCKPEYAYGSAGSPPDIPENATLIFEVELVACKPRKGSTFGSVSDEKARLEELKKQREIAAASKEEEKKRREEAKATAAARVQAKLEAKKGQGRGKGKSKGK 440 PeptidylprolylMGLGLKIASASFLPIFNIMATRSLCILLVCFIPVLAHVLSLQDPELGTVRVYFQ 38 781 isomeraseTTYGDIEFGFFPHVAPKTVEHIYKLVRLGCYNSNHFFRVDKGFVAQVADVVGGREVPLNSEQRKEGEKTIVGEFSEVKHVRGILSMGRYSDPDSASSSFSILLGNAPHLDGQYAVFGKVTKGDDTLKRLEEVPTRQEGIFVMPLERIRILSTYYYDTNERESNLTCDHEVSILKRRLVESAYEIEYQRRKCLP 441 PeptidylprolylMASKRSLRTMNVWPTLPPLVLLLLLCFSSMSSSVVAKKSDVSELQIGVKHKPKS 38 526 isomeraseCDIQAHKGDRIKVHYRGSLTDGTVFDSSFERGDPIEFELGSGQVIKGWDQGLLGMCVGEKRKLRIPSKLGYGAQGSPPKIPGGATLIFDTELVAVNGKGISNDGDSDL 442Peptidylprolyl MSGAPAERPISYFDITIGGKPIGRIVFSLYADLVPKTAENFRALCTGEKGIGKS 371158 isomerase GKPLCYAGSGFHRVIKGFMCQGGDFTAGNGTGGESIYGEKFEDEAFPVKHTKPFLLSMANAGKDTNGSQFFITVSQTPHLDDKHVVFGEVIKGKSIVRAIENYPTASGDVPTSPIIISACGVLSPDDPSLAASEETIGDSYEDYPEDDDSDVQNPEVALDIARKIRELGNKLFKEGQIELALKKYLKSIRYLDVHPVLPDDSPPELKDSYDALLAPLLLNSALAALRTQPADAQTAVKNATRALERLELSDADKAKALYREASAHVILKQEDEAEEDLVAASQLSPEDMAISSKLKEVKDEKKKKREKEKKAFKKMFSS 443 PeptidylprolylMASSLRSSLFSSWALDSKSVCSLFNLNPGKMGLPSISTPLNWRTCCCSHSSELL 61 768 isomeraseELNEGLQSSRRKTVMGLSTVIALSLVYCDEVGAVSTSKRALRSQKVPEDEYTTLPNGLKYYDLKVGSGTEAVKGSRVAVHYVAKWKGITFMTSRQGMGITGGTPYGFDVGASERGAVLKGLDLGVQGMRVGGQRILIVPPELAYGNTGIQEIPPNATLEFDVELISIKQSPEGSSVKIVEG 444 WD40 repeatMGAIEDEEPPLKRLKVSSPGLRRGLEEEAPSLSVGSVSILMAKSLSLEEGETVG 421 2172 proteinSKGLIRRVEFVRIITQALYSLGYQKAGALLEEESGILLQSSNVALFRKQILDGKWDESVVTLRGIDQVEVEGNTLKAASFLILQQKFFELLDKGNIPEAMKTLRLEISPMQLNTKRVHELASCIVFPSRCEELGYSKQGNPKSSQRMKVLQEIQQLLPPSIMIPEKRLERLVEQALNVQREACIFHNSLDPALSLYTDHQCGRDQIPTTTLQVLESHKNEVWFLQFSNNGKYLASASKDCSAIIWEITEGDSFSMKHRLSAHQKPVSFVAWSPDDKLLLTCGIEEVVKLWNVETGECKLTYDKANSGFTSCGWFPDGERFISGGVDKCIYIWDLEGKELDSWKGQGMPKISDLAVTSDGKEIISICGDNAIVMYNLDTKTERLIEEESGITSLCVSKDSRFLLLNLANQEIHLWDIGARSKLLLKYKGHRQGRYVIRSCFGGSDLAFVVSGSEDSQVYIWHRGNGELLAVLPGHSGTVNCVSWNPVNPHVFASASDDYTIRIWGVNRNTFRSKNASSSNGVVHLANGGP 445 WD40 repeatMPGTTAGAGIEPIEPQSLKKLSLKSLKRSFDLFASLHGEPQPPDQRSQRIRIAC 163 1647 proteinKVRAEYEVVKNLPTLPQREVGSSVSNSNVGETHSSLTTNQAQGFPTDTSGDLSKDEGKEITSIAVHLQPQTGLIDGKAGAIAGTSTAISSVGSSDRYQPSAAIMKRLPSKWPRPIWHPPWKNYRVISGHLGWVRSVAFDPGNEWFCTGSADRTIKIWEVATGKLKLTLTGHIEQIRGLAVSSRHPYLFSAGDDKQVKCWDLEYNKAIRSYHGHLSGVYCLALHPTLDILCTGGRDSVCRVWDIRTKAQIFALSGHENTVCSVFTQAIDPQVVTGSHDTTIKLWDLAAGKTMSTLTYHKKSVRAIAKHPFEHTFASASADNIKKFKLPKGEFLHNMLSQQKTIVNAMAINEDNVLVSAGDNGSLWFWDWKSGHNFQQAQTIVQPGSLDSEAGIYALQYDITGSRLVSCEADKTIKMWKEDETATPESHPINFK APKDIRRF 446 WD40repeat MRPILMKGHERPLTFLKYNRDGDLLFSCAKDHTPTVWYGHNGERLGTYRGHNGA 192 1172protein VWCCDVSRDSTRLITSSADQTAKLWNVETGAQLFSFNFESPARAVDLAIGDKLVVITTDPFMELPSAIHIKRIEKDLSKQTADSVLTITGIKGRINRAVWGPLNSTIISGGEDSVVRIWDSETGKLLRESDKETGHQKPITSLCKSADGSHFLTGSLDKSARLWDIRTLTLIKTYVTERPVNAVAISPLLDHVVIGGGQEASHVTTTDRRAGKFEAKFFHKILEEEIGGVKGHFGPINSLAFNPDGRSFASGGEDGYVRLHHFDPDYFHI KM 447 WD40repeat MRPILMKGHERPLTFLKYNRDGDLLFSCAKDHTPTVWYGHNGERLGTYRGHNGA 131 1111protein VWCCDVSRDSTRLITSSADQTAKLWNVETGNQLFSFNFESPARAVDLAIGDKLVVITTDPFMELPSAIHIKRIEKDLSKQTADSVLTITGIKGRINRAVWGPLNSTIISGGEDSVVRIWDSETGKLLRESDKETGHQKAITSLCKSADGSHFLTGSLDKSARLWDIRTLTLIKTYVTERPVNAVAISPLLDHVVIGGGQEASHVTTTDRRAGKFEAKFFHKILEEEIGGVKGHFGPINSLAFNPDGRSFASGGEDGYVRLHHFDPDYFHI KM 448 WD40repeat MAENNVGDFIPLDRQEYPSKPAPGAVDSSFWKSFKKKEVSRQIAGVTCINFCPE 149 1726protein PPHDFAVTSSTRVHIYDGKSCELKKTITKFKDVAYSGVFRSDSQIIAAGGETGVIQVFNAKSQMVLRQLKGHGRPVRVVRYSPQDKLHLLSGGDDSMVKWWDITTQEELLNLEGHKDYVRCGAASPSSVNLWATGSYDHTVRLWDLRNSKTVLQLKHGKPLEDVLFFPSGGLLATAGGNVVKVWDILGGGRPIHTMETHQKTVMAMCISKVPRSGQALGDAPSRLVTASLDGYMKVFDLDHFKVTHSARYPAPILSMGISSLCRTMAVGTSSGLLFIRQRKGQIEDKIHSDSSGLQVNPVNDEKDSAVLKPNQYRYYLRGRSEKPSEGDYVVKRMAKVYFQEYDKDLRHFNHSKALVSALKAADSKGTVAVIEELVARKRLIQTLSILNLDELELLINFLSRFILVPKYSRFLISLTDRVLDARAVDLGKSENLKKQIADLKGIVVQELRVQQSMQELQGIIEPLIRASAR 449 WD40 repeatMDVETSGKPTGNKRTYTRLPRQVCVFWQEGRCTRESCNFLHVDEPGSVKRGGAT 948 2228 proteinNGFAPKRSYNGSDERDTLAAGPPGGSRRNISARWGRGRGGIFISDERQKIRNKVCNYWLAGNCQRGEECKYLHSFVMGSDVKFLTQLSGHVKAIRGIAFPSDSGKLYSGGQDKKVIVWDCQTGQGTDIPLNDEVGCLMSEGPWIFVGLPNAVKAWNILTSTELSLVGPRGQVHALAVGNGMLFAGTHDGSILAWKFSPASNTFEPAASLVGHTQAVVSLVSGADRLYSGSMDKTIRVWDLGTFQCLQTLRDHTSVVMSLLCWDQFLLSCSLDNTVKVWVATSSGALEVTYTHNEEHGVLALCGMNDEQAKPVLLCSCNDNTVRLYDLPSFSERGRIFSRNEVRTFQIAPGGLFFTGDATGELKVWNWATQKS 450 WD40 repeatMSVQELRERHAAATAKVNALRERIKAKRLQLLDTDVATYASSNGRTPISFSFTD 332 1465 proteinLVCCRTLQGHTGKVYSLDWTSEKNRIVSASQDGRLIVWNALTSQKTHAIKLPCAWVMTCAFSPSGQAVACGGLDSVCSIFQLNNQLDRDGHLPVSRILSGHRSYVSSCQYVPDGDTHVITGSGDRTCIQWDVTTGQRIAIFGGEFPLGHTADVMSVSISAANPKEFVSGSCDTTTRLWDTRIASRAIRTFHGHEADVNTVKFFPDGLRFGSGSDDGTCRLFDIRTGHQLQVYRQPPRENQSPTVTAIAFSFSGRLLFAGYSNGDCFVWDTILEKVVLNLGELQNTHNGRISCLGLSADGSALCTGSWDKNLKIWAFGGHRKIV 451 WD40 repeatMKVKIISRSTDEFTRERSNDLQRVFRNFDPNLHTQARAQEYVRALNAAKLDKIF 232 1590 proteinAKPFLAAMSGHIDGISAMAKSPRHLKSIFSGSVDGDIRLWDIAARRTVQQFPGHRGAVRGLTVSTEGGRLISCGDDCTVRLWDIPVAGIGESSYGSENVQKPLATYVGKNSFRAVDYQWDSNVFATGGAQVDIWDHDRSEPTNSFAWGSDTVISVRFNPAEKDIFATTASDRSIVLYDLRMASPLNKLIMQTRNNAIAWNPREPMNFTAANEDCNCYSYDMRRMNISTCVHQDHVSAVMDIDYSPSGREFVTGSYDRTVRIFPYNAGHSREIYHTKRMQRVFCVKFSGDATYVVSGSDDANIRLWKAKASEQLGVLLPRERKRHEYLDAVKERFKHLPEIKRIERHRHLPKPIYKAALLRHTVNAAAKRKEERKRAHSAPGSVVTNPLRKKRIVAQLE 452 WD40 repeatMDHYYQDDFDYLVDDEMVDFADDVEDDVRTRRRSDIDSDSENDFDLNNKSPDTT 207 1550 proteinALQAKRGKDIQGIPWNRLNFTREKYRETRLQQYKNYENLPRPRRSRNLDKECTNFERGSSFYDFRHNTRSVKATIVHFQLRNLVWATSKHNVYLMQNYSIMHWSSLKQKGEEVLNVAGPIVPSVKHPGSSPQGLTRVQVSAMSVKDNLVVAGGFQGELICKYLDKPGVSFCTKISHDENGITNAVEIYNDASGATRLMTANNDLAVRVFDTEKFTVLERFSFPWSVNHTSVSPDGKLVAVLGDNADCLLADCKTGKTVGTLRGHLDYSFAAAWHPDGYILATGNQDTTCRLWDVRKLSSSLAVLKGRMGAIRSIRFSSDGRFMAMAEPADFVHLYDTRQNYTKSQEIDLFGEIAGISFSPDTEAFFVGVADRTYGSLL EFNRRRMNYYLDSIL453 WD40 repeat MAEALVLRGTMEGHTDAVTAIATPIDNSDMIVSSSRDKSILLWNLTKEPEKYGV221 1171 protein PRRRLTGHSHFVQDVVISSDGQFALSGSWDSELRLWDLNTGLTTRRFVGHTKDVLSVAFSIDNRQIVSASRDRTIKLWNTLGECKYTIQPDAEGHSNWISCVRFSPSATNPTIVSCSWDRTVKVWNLTNCKLRNTLVGHGGYVNTAAVSPDGSLCASGGKDGVTMLWDLAEGKRLYSLDAGDIIYALCFSPNRYWLCAATQQCVKIWDLESKSIVADLRPDFIPNKKAQIPYCTSLSWSADGSTLFSGYTDGKIRVWGIGHV 454 WD40 repeatMAAIKSTSRSASVAFAPDAPLLAAGTMAGAIDLSFSSLANLEIFKLDFQSDDPE 221 3679 proteinLPVVGECPSNERLNRLSWGSAGGSFGIIAGGLVDGTINIWNPATLINSEDNGDALIARLEQHTGPVRGLEFNTISTNLLASGAEDGELCIWDLANPTAPTHFPPLKGVGSGAQGEISFLAWNRKVQHILASTSYSGTTVVWDLRRQKPIISFPDATRRRCSVLQWNPDASTQLIVASDDDNSPTLRAWDLRNTISPYKEFVGHSRGVIAMSWCPSDSLFLLTCAKDNRTLCWDTGSGEIVCELPAGANWNFDVQWSPKIPGILSTSSFDGKIGIHNIEACSRNVSGEVEFGGAIVRGGPSALLKAPKWLERPAGVSFGFGGKLASFRPSTVAQAADHRHSEVFIHNLVTEDNLVIRSTEFEAAIADGEKVSLRALCDRKAEESQSDEEKETWNFLRVMFEDEGTARTKLLEHLGFKVQSEENGDLQETHSSKIDDIGSEIGKTLTLDDKTEEDVLPQLKGGQDAAIPQDNGEDFFDNLHSPKEEVSLSHVGNDFVGEKDKDMVVNGAEIEHETEDLTEYSDWNEAIQHSLVVGDYKGAVLQCLSANRMADALIIAHLGGNSLWEKTRDEYLKKAKSSYLKVVSAMVNNDLTGLVNSRPLKSWKETLAMLCTYSQREEWTVLCDMLASRLIAAGNVMAATLCYICAGNIEKTVEIWSRSLKYDYDGRSFVDHLQDVMEKTVVLALATGQKRVSPSLSKLVENYAELLASQGLLTTAMEYLKLLGTEESSHELSILRDRLYLSGTDNKVEASSFPFETRQDLTESQYNMHQTGFGAPETQKNYQENVHQVLPSGSYTDNYQPTANTHYIAGYQPAPQQQPSFQNYFTPASYQPAPSPNVFYPSQVSQAEQSNFAPPVNQPPMKTFVPSTPPILRNVDQYQTPSLNPQLYQGVSSATVETHPYQTGAPASVSVGTTPGQPSVVPNFMVPGPVTAPTVTPRGFMPVTTPTQHPLGSANPPVQPQSPQSSQVQSVTAATTPPPTIQNVDTSNVAAEIRPVIGTLRRLYDETSEALGGARANPAKRREIEDNSRKIGSLFAKLNSGDISSNAASKLVHLCQALESRDYATAFQIQVGLTTSDWDECSFWLAALKRMIKVKQNMR 455 WD40 repeatMAGAADSQLQTLSERDSTPNFKNLHTREYAAHKKKVHSVAWNCTGTKLASGSVD 269 1252 proteinQTARVWNIEPHGHSKTKDLELKGHADSVDQLCWDPKHSELLATASGDRTVRLWDARSGKCSQQVELSGENINITFKPDGTHIAVGNRDDELTIIDVRKFKPLHKRKFSYEVNEIAWNTTGELFFLTTGNGTVEVLSYPSLQVLHTLVAHTAGCYCIAIDPIGRYFAVGSADALVSLWDLSEMLCVRTFTKLEWPVRTISFNHDGQYIASASEDLFIDIADVQTGRTVHQISCRAAMNSVEWNPKYNLLAFAGDDKNKYMQDEGVFRVFGF ETP 456 WD40repeat MAATSPVGAGSGRELANPPTDGISNLRFSNHSDHLLVSSWDRKVRLYDASANSL 214 1242protein KGQFVHGGPVLDCCFHDDASGFSGSADNTVRRYDFSTRKEDILGRHEAPVRCVEYSYAAGQVITGSWDKTLKCWDPRGASGQEKTLVGTYSQLERVYSMSLVGHRLVVATAGRHINVYDLRNMSQPEQRRESSLKYQTRCVRCYPNGTGFALSSVEGRVAMEFFDLSEAGQAKKYAFKCHRKSEAGRDTVYPVNAIAFHPIYGTFATGGCDGYVNVWDGNNKKRLYQYSKYPTSIAALSFSRDGRLLAVASSYTFEEGEKPHEPDAVFVRSVNEAEVKPKPKVYAAPP 457 WD40 repeatMASDDEEGFKNEEAPGVVDEAEVQEGLRACFPLSFGKQEKKQAPLESIHSATKR 119 2065 proteinPEDPRPRRQLGPPRPPPSILAEQEDSDRFVGPPRPPQFVRDDNDDGEAEIMIGPPRPPAQYSDDHDNEETIGPPKPSYLEKGEETDQMVGPSKRGSDDETSGDSDDGDDAVDFRVPLSNEIVLRGHTKVVSALAIDQTGSRVLTGSYDYSVRMYDFQGMTSQLKSFRQLEPAEGHQVRSLSWSPTSDRFLCVTGSAQAKIFDRDGLTLGEFVKGDMYLRDLKNTKGHISGLTCGEWHPKEKQTILTCSEDGSLRIWDVNDFNTQKQVIKPKLAKPGRVPVTACAWGRDGKCIAGGVGDGSIQVWNLKPGWGSRPDLYVAKGHDDDITGLQFSADGNILLTRSTDETLKVWDLRKAITPLQVFRDLPNNYAQTNVAFSPDERLIFTGTSVERDGNSGGLLCFYDRQTLELVLRIGVSPVHSVVRCTWHPRHNQVFATVGDKKEGGAHILYDPALSERGALVCVARAPRKKSLDDFEAKPVIHNPHALPLFRDEPSRKRQREKARMDPMKSQRPDLPVTGPGFGGRVGSTKGSLLTQYLLKEGGLIKETWMEEDPREAILKYADVAAKDPKFIAPAYAQTQPETVFAETDSEEEQK 458 WD40 repeatMKERGQSHAGQPSVDERYTQWKSLVPVLYDWLANHNLVWPSLSCRWGPQMHQAT 186 1550 proteinYKNSQRLYLSEQTDGTVPNTLVIATCEVVKPRVAAAEHISQFNEEARSPFVKKFKTIIHPGEVNRIRELPQNSKIVATHTDGPDVLIWDVDTQPNRQATLGAADSRPDLVLTGHKDNAEFALAMSPSAPFVLSGGKDKCVLLWSIQDHISAATEPSSAKASKTPSSAHGEKVPKIPSIGPRGVYKGHKDTVEDVQFCPSNAQEFCSVGDDSALILWDARNGNEPVIKVEKAHNADLHCVDWNPHDENLILTGSADNSVRMFDRRNLTSSGVGSPVHKFEGHSAPVLCVQWCPDKASVFGSAAEDSYLNVWDYEKVGKNVGKKTPPGLFFQHAGHRDKVVDFHWNSFDPWTIVSVSDDGESTGGGGTLQIWRMSDLIYRPEDEVLAELERFRAHILSCQNK 459 WD40 repeatMSSLSRELVFLILQFLDEEKFKESVHKLEQESGFFFNMKYFDEKAQAGEWDEVE 244 3671 proteinRYLSGFTKVDDNRYSMKIFFEIRKQKYLEALDRQDRAKAVDILVKDLKVFSTFNEELYKEITQLLTLDNFRENEQLSKYGDTKSARTIMMSELKKLIEANPLFREKLIYPNLKASRLRTLINQSLNWQHQLCKNPRPNPDIKTLFTDHACGPPNGARTPTQPTASLGVLPKATTFTPIGPHGPFPSSSTATSGLASWMSNPNMVTSPQAPVAVGPSVPVPPNQATLLKRPRTPPGSSSVVDYQTADSEQLIKRLRPVSQSIDEATYPGPTLRVPWSTDDLPKTLARALNEPYPVTSIDFHPSQQTFLLVGTKNGEITLWEVGSREKLATRSFKIWDNANCSNHLEAAFVKDSSVSINRVLWSPDGTLIGIAFTKHLVHTYTFQGLDLRQHLEIDAHVGGVNDLAFSHPNKQLCVVTCGDDKMIKVWDAVTGRKLYNFEGHDAPVYSVCPHHKENIQFIFSTAVDGKIKAWLYDHLGSRVDYDAPGHSCTTMMYSADGTRLFSCGTSKEGESFLVEWNESEGAIKRTYSGLRKKGSGVVQFDTTQNHFLAVGDEHLIKFWDMDSTNMLTSCDAEGGLLNLPRLRFNKEGSLLAVTTVNGIKILANADGQKLLKTMENRTFDLPSRAHIDAASATSSPATGRMERIERTSSANTVSGINGVDPAQSSEKLRLSDDLSEKTKIWKLTEITDSIQCRCITLPENAAEPASKVSRLLYTNSGVGLLALGSNAVHKLWKWNRSEQNPSGKATASVHPQRWQPTSGLLMTNDITDINPEEAVPCIALSKNDSYVMSASGGKVSLFNMMTFKVMTTFMPPPPASTFLAFHPQDNNIIAIGMEDSTIHIYNVRVDEVKTKLKGHQKRITGLAFSSTQNILVSSGADAQLCVWNTETWEKRKSKTIQMPVGKTVSGDTRVQFHSDQLHILVVHETQLAIYDAYKLERQYQWVPQDALSAPILYATYSCNRQLIYATFSDGNIGVYDAEILRPRCRIAPTTYLSSGTSSSTSLPLVVAAHPHEPNQFAIGLSDGAVQVLEPSESEGKWGVSPPPENGVVPAVVAGPSTSNQGSEQAPR 460 WD40 repeatMAKDEEEFRGEMEERLVNEEYKIWKKNTPFLYDLVITHALEWPSLTVQWLPDRE 163 1431 proteinEPPGKDYSVQKMILGTHTSDNEPNYLMLAQVQLPLEDAENDARQYDDERGEIGGFGCANGKVQVIQQINHDGEVNRARYMPQNPFIIATKTVSAEVYVFDYSKHPSKPPQDGGCHPDLRLRGHNTEGYGLSWSPFKHGHLLSGSDDAQICLWDINVPAKNKVLEAQQIFKVHEGVVEDVAWHLRHEYLFGSVGDDRHLLIWDLRTSATNKPLHSVVAHQGEVNCLAFNPFNEWVLATGSADRTVKLFDLRKISSALHTFSCHKEEVFQIGWSPKNETILASCSADRRLMVWDLSRIDEFQTPEDALDGPPELLFIHGGHTSKISDFSWNPCEDWVIASVAEDNILQIWQMAENIYHDEEDDMPPEEVV 461 WD40 repeatMSPGVKQTGSQKFESGHQDVVHDVTMDYYGKRIATCSADRTIKLFGLNASDTPS 155 1081 proteinLLASLTGHEGPVWQVAWAHPKFGSMLASCSYDGRVIIWREGQQENEWSQVQVFKEHEASVNSISWAPNELGLCLACGSSDGSITVFTCREDGSWDKTKIDQAHQVGVTAVSWAPASAPGSLVGQPSDPIQKLVSGGCDNTAKVWKFYNGSWKLDCFPPLQMHTDWVRDVAWAPNLGLPKSTIASCSQDGKVVIWTQGKEGDKWEGRILNDFKIPVWRVNWSLTGNILAVADGNNSVTLWKEAVDGDWNQVTTVQ 462 WD40 repeatMSSGVKQTGSQKFESGHQDVVHDVTMDYYGKRIATCSADRTIKLFGMNTSDTPT 537 1463 proteinLLASLTGHEGPVWQVAWAHPKFGSMLASCSYDRRVIIWREGQQENEWSQVQVFKEHEASVNSISWAPHELGLCLACGSSDGSITVFTGREDGSWDKTKIDQAHQVGVTAVSWAPASAPGSLVGQPSDPVQKLVSGGCDNTAKVWKFYNGSWKLDCFPPLQMHTDWVRDVAWAPNLGLPKSTIASCSQDGRVVIWTQGKEGDKWEGKILNDFKTPVWRISWSLTGNILAVADGNNNVTLWKEAVDGEWNQVTTVQ 463 WD40 repeatMKKRSRPSNGHLSTAAKNKSRKTAPITKDPFFDSAHNRNKSKGKGKSRGKGEEI 284 1909 proteinFSSDEDDDAIGRDAPAEEEEEIAEEERETADEKRLRVAKAYLDKIRAITKANEEDNEEEAGEDEETEAERRGKRDSLVAEILQQEQLEESGRVQRQLASRVVTPSKLVECRVVKRHKQSVTAVALTEDDLRGFSASKDGTIIHWDVETGASEKYEWPSQAVSVSSSNEVSKTQKGKGSKKQGSKHVLSMAVSSDGRYLATGGLDRYIHLWDTRTQKHIQAFRGHRGAVSCLAFRQGTQQLISGSFDRTIKLWSAEDRAYMDTLYGHQSEILAVDCLRKERVLSVGRDHTLRLWKVPEETQLVFRGHAASLECCCFINNEDFLSGSDDGSIELWSMLRKKPVFMAKNAHGHAIVENLSEDTSTREEPDEEVTTRQLPNGNSIGNGMTNQMGITPSVESWVGAVTVCRGTDLAASGAGNGVVRLWAIENSSKSLRALHDIPLTGFVNSLTFARSGRFLIAGVGQEPRLGRWGRIQAARNGVTLCPIELS 464 WD40 repeatMAATFGTINTATSPHNPNKSFEIVQPPNDSISSLSFSPKANYLVATSWDNQVRC 610 1659 proteinWEVLQTGASMPKAAMSHDQPVLCSTWKDDGTAVFSAGCDKQAKMWPLLTGGQPVTVAMHDAPIKDIAWIPEMNLLATGSWDKTLKYWDTRQSNPVHTQQLPERCFALSVRHPLMVVGTADRNLIIFNLQNPQTEFKRISSPLKYQTRCVAAFPDKQGFLVGSIEGRVGVHHVEEAQQSKNFTFKCHRDSNDIYAVNSLNFHPVHQTFATAGSDGAFNFWDKDSKQRLKAMARSNQPTPCSTFNSDGSLYAYAVSYDWSKGAENHNPATAKHHILLHVPQESEIKGKPRVTTSGRK 465 WD40 repeatMVVMDKGTHQTNEDESESEFIDEDDVIDEISIDEEDLPDADVEGEDVQEDNKRS 241 1452 proteinEPDENSSSLDDAIHTFEGHEDTLFAVACSPVDATWVASGGGDDKAFMWRIGHATPFFELKGHTDSVVALSFSNDGLLLASGGLDGVVRIWDASTGNLIHVLDGPGGGIEWVRWHPKGHLVLAGSEDYSTWMWNADLGKCLSVYTGHCESVTCGDFTPDGKAICTGSADGSLRVWNPQTQESKLTVKGYPYHTEGLTCLSISSDSTLVVSGSTDGSVHVVNIKNGKVVASLVGHSGSIECVRFSPSLTWVATGGMDKKLMIWELQSSSLRCTCQHEEGVMRLSWSLSSQHIITSSLDGIVRLWDSRSGVCERVFEGHNDSIQDMVVTVDQRFILTGSDDTTAKVFEIGAF 466 WD40 repeatMPVFRTAFNGYAVKFSPFVETRLAVATAQNFGIIGNGRQHVLELTPNGIVEVCA 223 1173 proteinFDSSDGLYDCTWSEANENLVVSASGDGSVKIWDIALPPVANPIRSLEEHAREVYSVDWNLVRKDCFLSASWDDTIRLWTIDRPQSMRLFKEHTYCIYAAVWNPRHADVFASASGDCTVRIWDVREPNATIIIPAHEHEILSCDWNKYNDCMLVTGSVDKLIKVWDIRTYRTPMTVLEGHTYAIRRVKFSPHQESLIASCSYDMTTCMWDYRAPEDALLARYDHHTEFAVGIDISVLVEGLLASTGWDETVYVWQHGMDPRAC 467 WD40 repeatMDSRNRRSRLNLPPGMSPSSLHLETTAGSPGLSRVNSSPSTPSPSRTTTYSDRF 251 1777 proteinIPSRTGSRLNGFALIDKQPQPLPSPTRSAAEGRDDASSSSASAYSTLLRNELFGEDVVGPATPATPEKSTGLYGGSRDSIKSPMSPSRNLFRFKNDHGGNSPGSPYSASTVGSEGLFSSNVGTPPKPARKITRSPYKVLDAPALQDDFYLNLVDWSSNNVLAVGLGTCVYLWSACTSKVTKLCDLGVNDSVCSVGWTPQGTHLAVGTNIGEVQIWDTSRCKKVRTMGGHCTRAGALAWSSYILSSGSRDRNILHRDIRVQDDFIRKLVGHKSEVCGLKWSYDDRELASGGNDNQLLVWNQQSAQPLLRFNEHTAAVKAIAWSPHQHGILASGGGTADRCLRFWNTATDTRLNCVDTGSQVCNLVWCKNVNELVSTHGYSQNQIMVWRYPSMSKLATLTGHTLRVLYLAISPDGQTIVTGAGDETLRFWSIFPSPKSQSAVHDSGLWSLGRTHIR 468 WD40 repeatMEKKKVVVPIVCHGHSRPIVDLFYSPVTPDGLFLISASKDSSTMLRNGETGDWI 367 1419 proteinGTFEGHKGAVWSCCLDNRALRAASGSADFSAKIWDALTGDELHCFVHKHIVRACAFSESTSLLLTGGHEKILRIFDLNRPDAPPKEVDNSPGSIRTVAWLHSDQTILSSNSDAGGVRLWDLRTEKIVRVLETKSPVTSAEVSQDGRYITTADGNSVKFWDANHFGMVKSYTMPCMVESASLEPTMGNMFVAGGEDMWVRLFDFHTGEEIACNKGHHGPVHCVRFAPGGESYSSGSEDGTIRIWQTLNMNSEENESYGVNGLSGKVRVGVDDVVQKVEGFQITADGHLNDKPEKPNP 469 WD40 repeatMERYSQGTQKKSEIYTYEAPWQIYGMNWSVRKDKKFRLGIGSFLEEYNNRVEII 284 1303 proteinELDEESGEFKSDPRLAFDHPYPTTKIMFVPDKECQRPDLLATTGDYLRIWQVCEDRVEPKSLLNNNKNSEFCAPLTSFDWNDADPKRIGTSSIDTTCTIWDIEKEVVDTQLIAHDKEVYDIAWGEVGVFASVSADGSVRVFDLRDKEHSTIIYESSQPETPLLRLGWNKQDPRFIATILMDSCKVVILDIRFPTLPVAELQRHQASVNTIAWAPHSPCHICTAGDDSQALIWELSSVSQPLVEGGGLDPILAYTAAAEINQLQWSSMQPD WVAIAFSNEVQILRV470 WD40 repeat MQSENNLDESLHLREVQELQGHTDTVWAVAWNPVTGIDGAPSMLASCSGDKTVR684 1784 protein IWENTHTLNSTSPSWACKAVLEETHTRTVRSCAWSPNGKLLATASFDATTAIWENVGGEFECIASLEGHENEVKSVSWSASGMLLATCGRDKSVWIWDVQPGNEFECVSVLQGHTQDVKMVQWHPNRDILVSASYDNSIKVWAEDGDGDDWACMQTLGNSVSGHTSTVWAVSFNSSGDRMVSCSDDLTLMVWDTSINPAERSGNAGPWKHLCTISGYHDRTIFSVHWSRSGLIASGASDDCIRLFSESTDDSVTPVDGTSYKLILKKEKAHSMDVNSVQWHPSEPQLLASASDDGRIKIWEVTRINGLANSH 471 WD40 repeatMKRAYKLQEFVAHASNVNCLKIGKKSSRVLVTGGEDHKVNMWAIGKPNAILSLS 336 2738 proteinGHSSAVESVTFDSAEALVVAGAASGTIKLWDLEEAKIVRTLTGHRSNCISVDFHPFGEFFASGSLDTNLKIWDIRRKGCIHTYKGHTRGVNSIRFSPDGRWVVSGGEDNIVKLWDLTAGKLMHDFKCHEGQIQCMDFHPQEFLLATGSADRTVKFWDLETFELIGSAGPETTGVRAMIFNPDGRTLLTGLHESLKVFSWEPLRCYDAVDVGWSKLADLNIHEGKLLGCSYNQSCVGVWVVDISRVGPYAAGNVSRTNGHNEAKLASSGHPSVQQLDNNLKTNMARLSLSHSTESGIKEPKTTTSLTTTEGLSSTPQRAGIAFSSKNLPASSGPPSYVSTPKKNSTSRVQPTTNFQTLSRPDIVPVIVPRSNSLRPETTSDVKKEMNNFGRVVPSTVSTKSTDVIKSGSNRDESDKIDSINQKRMTGNDKTDLNIARAEQHVSSRLDNTNTSSVVCDGNQPAARWIGAAKFRRNSPVDPVVSPHDRSPTFPWSATDDGVTCQPDRQVTAPELSKRVVEPGRARALVASWETREKALTADTPVLVSGRPPTSPGVDMNSFIPRGSHGTSESDLTVSDDNSAIEELMQQHNAFTSILQARLTKLQVIRRFWQRNDLKGAIDATGKMGDHSVSADVISVLIERSEIFTLDICTVILPLLTRLLQSETDRHLTVAMETLLVLVKTFGDVIRATISATPTIGVDLQAEQRLERCNLCYVELENIKQILVPLIRRGGAVAKSAQELSLALQEV 472 WD40 repeatMSTLEIEARDVIKIVLQFCKENSLHQTFQTLQNECQVSLNTVDSLETFVADINS 81 1622 proteinGRWDVILPQVAQLKLPRKKLEDLYEQIVLEMIELRELDTARAILRQTQAMGFMKQEQPERYLRLEHLLVRTYFDPREAYHESSKEKRRSQIAQALASEVTVVPPSRLMALIGQSLKWQQHQGLLPPGTQFDLFRGTAAVKADEEEMYPTTLAHTIKFGKQSHPECARFSPDGQYLVSCSVDGFIEVWDYISGKLKKDLQYQADDSFMMHDDAVLCVDFSRDSEMLASGSQDGKIKVWRIRTGQCLRRLERAHSQGVTSLSFSRDGSQLLSTSFDSTARIHGLKSGKALKEFRGHTSYVNDAIFTSDGGRVITASSDCTVKVWDVKTTDCIQTFKPPPPLKGGDVSVNSVHLFPKNSEHIVVCNKASSIYIMTLQGQVVKSFSSGKREGGDFVAACISPKGEWIYCVGEDRNIYCFSQQSGKLEHLMKAHDKDIIGVTPHPHRNLLVTYSEDSTMKIWKP 473 WD40 repeatMDIELEDQPFDLDFHPSAPIVAVALITGRLQLFRYVDISSEPERLWTVTAHTES 399 1460 proteinCRAARFINAGSSVLTASPDCSILATNVETGQPVARLDNAHGAAINCLTNLTESTIASGDENGIIKVWDTRQNSCCNKFKAHEDYISDMEFVPDTMQLLGTSGDGTLSVCNLRKNKVHARSEFSEDELLSVALMKNGKKVVCGSQEGVLLLYSWGYFKDCSDRFVGHPHSVDALLKLDEDTVLTGSSDGIIRVVSILPNKMIGVIGEHSSYPIERLAFSHDRNVLGSASHDQILKLWDIHYLHEDDEPETNKQEAVNDENVDMDLDVDTEKRPRGSKRKKRAEKGQTSSQKQSSDFFADI 474 WD40 repeatMDRIQQIPHTCVARKINLPLGMSKESLALNLPANLAPTMSPPSITYSDRFIPSR 207 1673 proteinKASNFEEFALPDKTSPSPNSAGGQSSSTNGEGRDDACAAYSALLRTELFPATPDKTEGCRRPVIGSPSGNVFRFKSQQCKSQSPFSLCPVGEDGDLSETGAVARKTTRKIPRSPFKVLDAPALQDDFYLNLVDWSSHNILAVGLSACVYLWSASSSKVTKLCDLGLDDNVCSVAWTQRGTYLAVGTNNGGVQIWDAAHCKQVRTMEGHCTRVGTLAWNSHILSSGGRDRNILQRDIRAQDDFVSKFSGHKSEVCGLKWSYDNRELASGGNDNQLFVWNQQSQQPVLKYNEHTAAVKAIAWSPHQHGLLASGGGTADRCIRFWNTATNTSLNCVDTGSQVCNLVWSKNVNELVSTHGYSQNQIIVWRYPTMSKLATLTGHTLRVLYLAISPDGQTIVTGAGDETLRFWNVFPSSKTQQNTIRDMGVWSSGRTH IR 475 WD40repeat MAGGQGEGEEKVDKLSMELTEDVMKSMEIGAVFKDYNGKINSLDFHRTNNYLVT 263 1309protein ASDDEAIRLFDTASATWQKTSYSKKYGVDLICFTNHQTSVLYSSKNGWDESLRHLSLMDNKYLRYFKGHHDRVVSLCMSPKGECFMSGSLDRTVLLWDLRIDKCQGLIRVRGRPAVAYDEQGLVFAISNEGGLIKMFDARLYDKGPFDTFVVEGDKSEASGIKFSNDGKLILLSTMDSNIHVLDAYQGTTVHSFSVEAVPNGGEAVPNGGTLEASFSPDGKFVISGSGNGNIHAWSVNSGKEVACWTTEGVIPAVVKWAPRRLMFASGSSVLSLWVPDLSKLASLTGSNSNSAY 476 WD40 repeatMHRVGSTGNTSNSSRPRREKRLTYVLNDANDSRHCSGINCLVISKLSLLGGNDY 232 2529 proteinLFSGSRDGTLKRWELADDSAVCSATFESHVDWVNDAVLTGETLVSCSSDTTLKTWRPFSDGVCTRTLRQHSDYVTCLAAASKNSNIVASGGLGREVFIWDIEAAMAPVSRTSEAMDDDTSNGVLSSGNSVLSTTVRSTNATNSASLHTSQLQGYTPIAAKGHKESVYALAMNDVGTLLVSGGTEKVVRVWDPRSGAKQMKLRGHTDNVRALILDSTGRFCLSGSSDSIIRLWDLGQQRCVHSYAVHTDSVWALASTPNFSHVYSGGRDLSLYLTDLTTRESLLLCMEKHPLLRLTLQDDSIWVATTDSSLHRWPAEGQNPPKMFQRGGSFLAGNLSFTRARACLEGSAPVPVNTQPSFVIPGSPGIVQHEILNNRRHVLTKDAEGTVKLWEITRGAVLDDYGKVSFEEKKEELFEMVSIPAWFTMDTRLGSMSVHLDTPQCFTAEMYAVDLNVPDAPEEQKINLAQETLRGLLAHWLSRRRQRLATQASANGDFPAGQENALRNHISSRIDVHDDAETHIAGILPAFDFSTTSPPSIITEGSQGGPWRKKITDLDGTEDEKDFPWWCLECVLHGRLSPRESLKCSFYLHPYEGTTVQVLTQGKLSAPRILRIQKVINYVLEKMVLDRPLDSSNSETTFTPGLSGNQSHAAVVGDGSLRSGARVWQQKAKPLVEILCNNQVLSPDMSLATVRTYIWKKPDDLY LYYRLVQNR 477WD40 repeat MMKGKTIQMQAAHQNHDGETSVACVLWDWHAKHLITAGADNTILIHSYPSSSSS 562950 protein KPITLRHHKNAVTALAINSNVRSLASGSVDHSVKLYSYPGGEFQSNVTRFTLPIRSLAFNKSGELLAAAGDDEGIKLISTIDNSIARVLKGHNGPVTSISFDPKNEFLASSDSDGTVIYWELSTGKPVHTLKKIAPNTTSNPTSLNQISWRPDGEMLAVPGRKSEVSMYDRDTAEKLFSLKGGHSDTICSLAWSPNGKYIATAGTDRQVMVWDADRRQDIDKQRFDNPICSVAWKPSDNALAVIDVLGRFGVWESPIASHMKSPADGAERYDNMEDEEPLMARYEEELEDSVSGSLNEIINDDDDDDEMGKIPRKILQKKPSVKVEKGKEESNAKAFKSGQDSFKLKSAMQEAFQPGATQRQSGKRNFLAYNMLGSVITFDNDGFSHIEVDFHDIGKGCRVPSMTDYFGFTMASLSESGSVFGSPQKGEKNPSTLMYRPFSSWANNSEWSMRFPMGEEVKAVALGSGWVAAVTSLNFLRVFSEGGLQKFVLSMDGPVVTAAGYENLLVVVSHASNPLLSGDQVLSFTVYDISQKTCPLSGRLPLSPGSHLTWLGFSEEGLLSSYDSEGNLRVFTNDYNGCWVPIFSAARERKSETESIWMVGLNSTQVFCVVCKLPDTYPQVAPKPVLSVLNLSLPLACSDLGADDLENEYLRGSLLLSQMQKKAEDAVACGRESNMEEDSIFKMEAALDRCLLRLIANCCKGDKLVRATELARLLSLEKSLQGAIKLVSAMKLPMLAERFNTILEEKILQENMETISCRRLTSEAQDMDTPISISVKQVSYGANLGDSPFLPNRQVEPKHSTPVFSKPDTKIEVDTSEAIAKGCDAQNGNIKSGDAEVQPASHNDSIQKPSNPFAKASNTSANQAVQRNASLLSSIKQMKTATENEGKRKERARSGSLPQKPAKQSKIS 478 WD40 repeatMKQKRKGHQVDDPKYSVQTPQEDDTPNESGPASEEVESSDEEGGNSSNIEDDII 193 2577 proteinYSSSEEDPVVSSDYEEDEDAESDAEGVTAEQELEGDIDNALQNYMGTLTVLSNFHGENLKNAEGEDTSGDDDDEEEMPKRAEESDSPEDENDERPKRAEESDFSEDEDEERPKRAEESDSSEDEVPSRNTVGDVPLRWYKDEQHIGYDIKGKKIKKQPKKDQLDSFLASTDDSSDWRKVYDEYNDEEVELTKDEIKFISRLRKGTIPHADVNPYEPYVDWFDWKDKGHPLSNAPEPKRRFIPSKWEAKKVVKLVRAIRKGWITFQKAEEKPRFYLMWGDDLKPSEKMANGLSYIPAPKPKLPGHEESYNPPPEYIPTQEEINSYQLMYEEDRPKFIPKRFDSLRNVPAYDRFLSEIFERCLDLYLCPRTRKKRINIDPESLIPKLPKPKDLQPFPSICFLEYKGHTGAVSCISPESSGQWLASGSKDGTVRIWEVETARCLKVWDIGRPIQHIAWNPVSQLSILAVAVDEEVLVLNTGLGSEDSQEKVAELLHVKSKPVSADDLGDNTSLTKWIKHEKFDGIKLTHLKPVHLISWHHKGDYFATVAPDGNTRAVLVHQLSKQQTQNPFKKMQGRVVHVLFHPSRAIFFVATKTHVRVYDLVKQQLVKRLVTGLHEVSSMAVHHKGDNLLVGSKEGKVCWFDMDLSTQPYKTLKNHSKDIHSVAFHDSYPLFASCSDDCKAYVFYGLVYSDLLQNPLIVPLKVLQGHQSVNGMGVLDCQFHPKQPWLFTAGADSVVKLYCN 479 WD40 repeatMMSLKRGFEESLVPAKRQKTELSTVTYGDGPRRTSSLESPIMLLTGHHAAIYTM 187 1233 proteinKFNPTGTVIASGSHEREIFLWNVHGDCKNFMVLKGHKNAVLDLHWTTDGCQIISASPDKTLRAWDVETGKQIKKMAEHSSFVNSCCPSRRGPPLVVSGSDDGTAKLWDLRHRGAIQTFPDKYQITAVGFSDAADKIYSGGIDNEIKVWDLRRGEVTMRLQGHTDTITGMQLSSDGSYLLTNSMDCSLRIWDMRPYAPQNRCVKILTGHQHNFEKNLLKCSWSSDGSKVTAGSADRMVYIWDTTTRRILYKLPGHTGSVNETGFHPTQPIIGSCSSDKQIYLGEIEPNVGYQAVI 480 WD40 repeatMEFSDTYKHTGPCCFSPDARYLAIAVDYRLVIRDVVTLKVVQLYSCMDKISNIE 51 1436 proteinWALDSEYILCGLYKRAMVQAWSLSQPEWTCKIDEGPAGIAHARWSPDSRHIITTSDFQLRLTVWSLVNTACIHIQWPKHASKGVSFTQDGKFAAIATRRDCKDYVNLLSCHTWEVMGTFTVDTIDLADLEWSPNDSAIVVWDSPLEYKVLIYSPDGRCLFKYQAYDSWLGVKTVAWSPCSQFLAVGSYDQTLRTLNHLTWKPFAEFVHVSTVRGPASAVVFKEVEEPWNLDVSGLHLNDDNAHDIQDGKPAEGHSRVRYKVVEFPVNVSSQKHPVDKPNPKQGIGLLAWSRDSQYLFTRNDNMPTALWIWDICRLELAALLIQKEPIRAAAWDPVYPRVALCTGSSHLYMWTPSGACCVNIPLPQFVVSDLKWNPDGTSMLLKDRESFCCTFVPMLPEFNDDETNEE 481 WD40 repeatMAKLIETHSCVPSTERGRGILIAGDAKTNSIIYCNGRSVIMRNLDNPLEASVYG 525 2351 proteinEHSYPATVARFSPNGEWVASGDTSGTVRIWGRGSDHTLKYEYKALAGRIDDLEWSADGQRIVVCGDSKGKSMVRAFMWDSGTNVGEFDGHSRRVLSCSFKPTRPFRVATCGEDFLVNFYEGPPFRFKTSHRDHSNYVNCVRFAPDGSKFITVGSDRKGVIFDGKMGEKIGELSKEGGHTGSIYAASWSPDSKQVLTVSADKSAKIWEISETGNGTVKKTLTFGSQGGADDMLVGCLWLNDYLITVSLGGIVSLLSAVDPDKPPKTISGHMKSINAIALSLQSGQSEVCSSSYDGVIVRWILGVGYAGRVERKDSTQIKCLATIEGELVTCGFDNKVRRVPLLSEQHKESEPIDIGAQPKDLDVAVGCPELTFVSTDAGIIIIRASKIVSTTNVGYAVTAAAISPDGTEAVVGGQDGKLRVYSIKGDTLLEESVLERHRGPINAIRFSPDGSMFASGDLNREAVVWDRITREVKLKNMVYHTARINCIAWSPDSSKVATGSLDTCILIYEVGKPASSRITIKGAHLGGVYGLAFSDQSTVI SAGEDACVRVWSLP482 WD40 repeat MPQPSVILATAGYDHTVRFWEATSGRCYRTLQYPDSQVNHLEITPDKQYLAAAG152 1099 protein NPHIRLFEVNSNNPQPVISYDSHTNNVTAVGFQCDGKWMYSGSEDGTVKIWDLRAPGFQREYESRAAVNTVVLHPNQTELISGDQNGNIRVWDLNANSCSCELVPEDTAVRSLTVMWDGSLVVAANNHGTCYVWRLMRGTQTMTNFEPLHKLQAHNSYILKCLLSPEFCEHHRYLATTSSDQTVKIWNVDGFTLERTLTGHQRWVWDCVFSVDGAFLVTASSDSTARLWDLSTGEAIRTYQGHHKATVCCALHDGTDGASC 483 WD40 repeatMLTKFETKSNRVKGLSFHPKRPWILASLHSGVIQLWDYRMGTLIDKFDEHDGPV 470 4114 proteinRGVHFHKTQPLFVSGGDDYKIKVWNYKMRQCLFTFVGHLDYIRTVHFHNEYPWIVSASDDQTIRLWNWQSRVCISVLTGHNHYVMSASFHPKEDLVVSASLDQTVRVWDISGLRKKTVSPADDLSRLAQMNTDLFGGGDVVVKYVLEGHDRGVNWAAFGTSLPLIVSGADRQVGKLWRMNDTKAWEVDTLRGHTNNVSCVIFHARQDIIVSNSEDKSIRVWDMSKRTSVQTFRREHDRFWILAAHPEMNLLAAGHDSGMIVFKLERERPAYVVYGGSLLYVKDRYLRTYEFATQKDNPLIPIRKPGSIGPNQGPRSLSYSPTENAILICSDADGGAYELYAVPKDSHGRSDTVQEAKKGLGGSAVGVARNRFAVLDKNHNQVTIKNLKNEVTKKFDLPVTADALFYAGTGNLLCRSEDSVFLFDMQQRTVLGEIQTPNVRYVVWSNDMENVALLSKHTIIIASKKLSSTCSLHETIRVKSGAWDDNGIFMYSTLNHIKYCLPNGDSGIIKTLDVPVYITKVSGKSLYCLDRDGKNRVIQIDITECLFKLALSKKKYDYVINMIRNSQLCGQAIIAYLQQKGFPEVALHFVRDERTRFNLAVESGNIEIAVASAKEIDEKDHWYRLGVEALRQGNAGIVEYAYQRTKNFERLSFLYLITGNLDKLSKMLRIAEMKNDVMGQFHNALYLGDIQERIKILEESGHLHLAYATASLHGLADIADRLAADLGGNIPVLPPGKKSSLLMPPAPILHGGDWPLLRVTKGIFEGGLENSTSAAYEEEDEEAAADWGEDIDIENIEGENGEATVLDDQEVKGGEDDEGGWDMEDLELPPDVAAANVGTNQKTLFVAPTLGMPVSQIWMQKSSLAGEHAAAGNFETALRLLTRQLGIKNFSPLKPLFLELYMGSHTFLPSFASVPAFSLALQRGWSESASPNIRGPPALVYRLSVLEEKLTVAYRATTEGRFSEALRLFLNILHTIPVIVVDSRKEIDEVKELIGIAKEYVLGLRMEVKRKEIRDDAVRQQELAAYFTHCNLQKAHLKLALLNAMGISYRCKNYNTAANFARRLLETDPSSNHATKARQVLQVCERNLQDATQLNYDFRNPFVVCGATFTPIYRGQKEVSCPYCMARFVPDIAGKLCSICDLAIVGSDASGLFCFATQTR 484 WD40 repeatMDLLQNYQDDSEDSNPELRNHPPLEDATATSAPAGVENETSSSPDSSPLRLALP 196 2007 proteinAKSCAPDVDETLMALGVPGSEKKNNHNKPIDPTQHSVTFNPSYDQLWAPLYGPAHPYAKDGIAQGMRNHKLGFVEDSAIEPFMFDEQYNTFHRYGYAADPSASLGSHIVGDLESLKKNDGASVYNLPKREHKRQKLEKKMIQKDENEEEEKEVGEEVDNPSTEEWLKKNRKSPWAGKKEGLQTELTEEQKKYAQEHAEKKGDREKGEKVEIVDKTTFHGKEERDYQGRSWIDPPKDAKATNDHCYIPKRWVHTWSGHTKGVSAIRFFPKYGHLLLSAGMDTKVKIWDVFNSGKCMRTYMGHSKAVRDISFSNDGSRFLSAGYDRNIKLWDTETGKVISTFSTGKIPYVVKLHPDEDKQNVLLAGMSDKKIVQWDMNSGEITQEYDQHLGAVNTITFVDNNRRFVTSSDDKSLRVWEFGIPVVIKYISEPHMHSMPSISLHPNTNWLAAQSLDNQILIYSTRERFQLNKKKRFAGHIAAGYACQVNFSPDGRFVMSGDGEGRCWFWDWKTCKVFRTLKCHDNVCIGCEWHPLEQSKVATCG WDGMIKYWD 485WD40 repeat MARKGLGTDPAIGSLMSSKKRKEYKVTNRFQEGKRPLYAIAFNFIDARYHNIFA 2141323 protein TAGGTRVTIYQCLEGGAISVLQAYVDDDKDESFYTLSWACDVNGSPLLVAGGHNGIIRVLDVANEKVHKSFVGHGDSVNEIRTQALKPSLILSASKDESVRLWNVQTGICILIFAGAGGHRNEVLSVDFHPSDVYRIASCGMDNTVKIWSMKEFWTYVEKSFTWTDLPSKFPTKYVQFPVFIAAVHSNYVDCTRWLGNFILSKSVDNEVVLWEPYSKEQSTSDGVVDILQKYPVPECDIWFIKFSCDFHYNSMAVGNREGKVYVWELQSSPPNLIARLSHAHCKNPIRQTAISHDGSTILCCCDDGSMWRWDVVQ 486 WD40 repeatMESGAGGSVGARVPSAKPEMLQQPPYSNGDDDNDMERGTAPVPSSNPNTVSKWE 68 2146 proteinLDKDFLCPICMQTMKDAFLTACGHSFCYMCIMTHLNNKSNCPCCSLYLTNNQLFPNFLLNKLLKKTSACQMASTASPVENLCLSLQQGAEVSVKELDFLLTLLAEKKRKMEQEEAETNMEILLDFLQRLRQQKQAELNEVQADLHYIKDDILALEKRRLELSRARERYSRKLHMLLDDPMDTTLGHAAIDDGNNVRTAFVRGGQGDAISGKFQQKKAEIKAQASSQGMQKRANFCHSDSQVLPTLSGLTIARKRRVLAQFDDLQECYLQKRRRWATQLRKQCDGGLRKERDGNSISREGYHAGLEEFQSILTTFTRYSRLRVISELRHGDLFHSANIVSSIEFDRDDELFATAGVSRRIKVFDFATVVNEPADVHCPVVEMSTRSKLSCLSWNKCIKSQIASSDYEGIVTVWDVNTRQSVMMYEEHEKRAWSVDFSRTEPTRLISGSDDGKVKVWCTRQETSVLNIDMKANICCVKYNPGSSYYVAVGSADHHIHYYDLRNPSVPLYEFNGHRKTVSYVKFISTNELASASTDSTLRLWDVRDNCLVRTFKGHTNEKNFVGLTVNSEYIACGSETNGVFVYHKAISKPAAWHQFGSPDLDDSDDDTSHFISAVCWKSESPTMLAANSQGTIKVLVLAP 487 WD40 repeatMANYVDSKKNFKCVPALQQFYTGGPFRLSSDGSFLVCACNDEVKVVDLATGSVK 874 3705 proteinNTLEGDSELIVALALTPDNKYLFSASRSTQIKRWDLSSATCKRTWKAHNGPVADMACDASGGLLATAGADRSILVWDVDGGYCTHSFRGHQGVVTTVIFHPDPHCLLLFSGSDDATVRIWDLVAKKCISVLEKHFSTVTSLAISENGWNLLSAGRDKVVNIWDLRDYHCRATIPTYEPLEAVCVLPTGSRLVSVMNQSRALPENRKKSGAAPVYFLTVGERGIVRIWYSEGALCLYEQKSSDAIISSDKDELKGGFVSAVLLPLTQGVMCVTADQRFLFYNLDESDEGKCDLKVSKRLIGYNEEIVDLKFLGDEEKFLAVATNLEQVRMYDLSSMTCVYELSGHTDIVLCLDTVVFSGHSLLASGSKDHTVRIWDTESKSCICVAAGHMGAVGAVAFSKKAKNFFVSGSSDRTIKVWSFASVLDFGGISKSIKLSSQAAVAAHDKDINSVAVAPNDSLICTGSQDRTARIWRLPDLVPVLVLRGHKRGVWCVEFSPVDQCVMTASGDKTIKIWALSDGSCLKTFEGHTASVLRASFLTRGTQFVSSGADGLLKLWTIKSNECIATFDQHEDKIWAMAVGKKTEMLATGGSDSLVNLWHDCTTTDEEEALLKEEEAALKDQELLNALADTDYVKAIQLAFELRRPYKLLNVFTELYSKGHAQDQIQKVIRELGNEELRLLLEYVREWNTKPKFAHVAQFVLFQLFNVLPPKEIIEVQGISELLEGLIPYAQRHYSRIDRLMRSTFLLDYTLSSMSVLSPTETDLSSSNLLARTADPLHAQIDQFHPTHFPEPNLTPIQSLLDSGNTDSVEVTARRAKKKRVSGNDSEKTTVAEVKIGDMENAFDEPDVADQGSSRKHKPASSKKRKSIAVGNASIKRIASGNAVTIALQV 488 WD40 repeatMESSCSSMNSNRHSTEKRCLRPLQKQGASMNKHSSDRFIPARGSIDLDVARFMV 360 1754 proteinTQKQKDNNDIHALSPSPSPSKKAYQKEMADTLLKNAGAADNNCRILSFNGKSSTVSQGSQENVLANLSISRRARRYIPQSADRTLDAPDLLDDYYLNLLDWSSTNVLSTALGNTVYLWDASNSSISELLIADEEEGPVTSVSWAPDGSQIAVGLNNSVVQLWDSQSNKKLRALKGHHDRVGALSWNGPILTTGGLDGIIINHDVRTRDHIVQTYKGHTQEVCGLKWSPSGQQLASGGNDNLLYIWDKSMASHNPSSQYFHQLDEHCAAVKALAWCPFQTNLLASGGGTSDGSIKFWNTQTGACLNTVDTHSQVCSLLWNRHERELLSSHGLNQNQLTLWKYPSMVKITELTGHTARVLHMAQSPDGYTVASAAADETLKFWQVFGAPDASKKTKTKDTKGAFNMFHMHIR 489 WD40 repeatMLDEIVADEEEEFNIWKKNTPLLYDVVITHALEWPSLTVQWLPDRHQSPTKDYS 185 1384 proteinLQKMIVGTHTSGDEPNYLMIAEVQMPLQYSEDGNVGGFESTEAKVHIIQQINHEGEVNRAQYMPQNSFIIATKTVSSDVYVFDYTKHSSNAPQERVCNPELILKGHTNEGYSLSWSPLKEGQLLSGSNDAQICFWDINAASGRKVVEAKQIFKVHEGAVEDVSWHLKHEYLFGSVGDDCHLLIWDTRTAAPNKPQHSVVAHESEVNSLAFNPFNEWLLATGSADKTVKLFKLRKLSCSLFTFSNHTEEVFQIEWSPMNETILASSGGDRRLMVWDLRRIGDEQTSEDAEDGPPELIFIHGGHTSKISDFSWNLHDDWLIASSAEDNILQIWQMAENIYHDDADIL 490 WD40 repeatMTKEDHGESRDEMGERMVNEEYKLWKKNTPFLYDLVITHALEWPSLTVQWLPPS 241 1533 proteinCKQQQDIIKDDDIDHPNTQMVILGTHTSDNEPNYLILAEVQLHDGTEDEDGDGDVKRPQDKMKPGTSGGAMGKVRILQQINHQKEVNRARYMPQKPTIIATKTVNADVYVFDYSKHPSKPPQEGRCNPELRLQGHESEGYGLSWSPLKEGHLLSASDDAQICLWDITAATKAPKVVEANQIFRYHDGPVEDVAWHAIHDHLFGSVGDDHHLLLWDIRNDSEKPLHIVEAHQAEVNCLAFNPFNEWIVATGSADRTVALHDIRKLDKVLHTCAHHMEEVFQIGWSPQNGAILASCGSDRRLMVWDLSRIGDEQNPEDAEEAPPELLFIHGGHTSKISDFSWNPAEEWVIASVAEDNILQVWQMSEHIYNDDNDSPTA 491 WD40 repeatMAMAMGDENAADPVEEFNIWKKNTPFLYDLVITHALEWPSLTVQWLPDRHQSST 230 1435 proteinADYSLQKMIVGTHTSEDEPNYLMIAEVQIPLQNSSEDNIIGGFESTEAKVQIIQKINHEGEVNKARYMPQNSFVIATKTVSSDVYVFDYSKHPSKAPQERVCNPELILKGHSNEGYGLSWSPLKEGYLLSGSNDAQICLWDINAAFGKKVLEANQIFKVHEGAVGDVSWHLKHEYLFGSVGDDCHLLIWDMRTAAPNKPQQSVIAHQSEVNSLAFNPFNEWLLATGSMDKTVKLFDLRKLSCSLHTFSNHSTDQVFQIEWSPMNETILASSGADRRLMVWDLARIGETPEDEEDGPPELLFVHGGHTSKISDFSWNLNDDRVIASVAEDNILQIWQMAENIYHDDEDML 492 WD40 repeatMGLFEPFRALGYITDGVPFAVQRRGIETFVTLSVGKAWQIYNCAKLIPVLVGPQ 101 2857 proteinMDKKIRALACWRDFTFAATGHDIAVFRRAHQVATWSGHKAKVTLLLSFGQHVLSVDLEGCLFIWAVAEVNQNKPPIGQIQLGEKFSPSCIMHPDTYLNKVLIGSEEGTLQLWNVNTRKKLYEFKGWGSSIRCCVSSPALDVVGIGCSDGKIHVHNLRYDEEIVTFMHSTRGAVTALSFRTDGQPLLAAGGSSGVISIWNLEKKKLQSVIKDAHDSSVCSLHFFANEPVLMSSATDNSIKMWIFDTTDGEARLLKYRSGHSAPPMCIRYYGKGRHILSAGQDRAFRIFSVIQDQQSRELSQGHVGKRAKKLKVKDEEIKLPPVIAFDAAEIRERDWCNVVTCHLDDPCAYTWRLQNFVIGEHILKPCLEDPTPVKSCSISACGNFAVLGTEGGWLERFNLQSGISRGTYIDIGEKRQCAHNGAVVGLACDATNTLLISGGYNGDIKVWDFKGRELKFRWEIEVPLIKIVYHPGNGILATAADDMILRLFDVTAMRLVRIFVGHMDRVTDLCFSGDGKWLLSSSMDGTIRVWDIISSRQLNAMHMDSAVTALSLSPGMDMLATTHVGHNGIYLWANRMIYSKATDIEPFISGKQVVKVSMPTVSSKRESEEGDEKRTIVAESNVNKSDVSGSLIGDSYSAQLTPELVTLALLPKAQWQSLVNLDIIKMRNKPIEPPKKPEKAPFFLPSLPTLSGERIFIPSSMNGDGDQDETRNDKTVFEARGKKLGGESLSFMQLLQSCAKIKDFTTFTNYLKGLSPSAVDMELRLLQIVDNENISETEHSVELQGIGMLLDYFVNEVSCNNNFEFVQALIRLFLKIHGETIRCQVSLQEKARKLLEIQSSTWERLDTSFQNARCMITFLSSSQF 493 WD40 repeatMIAAVCWVPKGVAKVLPDSAEPPTQEEIQELLKCNVVAESDDNEDSDEESEEMD 43 1548 proteinTETDKNTDAVAKALAAANALGSQSSDFQRQHKVDDIANGLKELDMDHYDDEDEGIDIFGSGSLGNCYYPANDMDPYLVEQDDDDEDEIEDMTIKPSDLIILSARNEDDVSHLEVWIYEEETEEGGSNMYVHHDIILPAFPLSLAWLDCNLKGGEKGNFVAVGTMQPEIELWDLDVLDEVEPAVVLGGAVKDEASGKTTKLKKKKKNKQAVNFKEGSHTDAVLGLAWNMEYRNVLASASADKSVKIWDIVAEKCEHTMQPHTDKVQAVAWNPNQATVLLSGSFDRSVIMMDMRAPTHSGIRWPVPADVESLAWDPHTDHSFMVSAEDGTVRGFDIRAAASTADFDGKPMFILHAHDKAVCAISYNPAAPSLLTTGSTDKMVKLWDITNNQPSCIASTNPNVGAVFSAAFSKNSPFLLATGGSKGILHVWDTLD NSEVARRFGKFRPQN494 WEE1-like MIMDENEFCDIFSLRKRLCLLSSQEGEEEEELEAMSQLDAGEFTVTGNEEVVAI 2061657 protein AEDDVNTGILSQDLFSSQDYCTPSQPQDSTDLDSKDKAPCPLSPVKSTIQRKRCRPELLSNPPDSIQFSFQRLERVRSEESIQSSSQQLARVRSEVSSSDDFKTPKITASGQKNYVSQSALALRARVMSPPCIKNPYLDENEELNEKIQRSTRRSPACVTPIQSGACLSRYRADFHELEEIGRGNFSRVYKALNRLDGCCYAVKCSQSELRLDTERKVALMEVQSLAALGPHKNIVGYHTAWFENDHLYIQMELCDHNLTTANDRGILRTDTDFLEAVYQIAQALEFIHGRGVAHLDVKPENIYVRDGTYKLGDFGRATLINGTLHVEEGDARYMSREILNDNYEHLDKVDMFSLGATFFELLMRKQYPGSGKRIDRDTEIKIPILPGFSIYFQKLLQDLVSNDPGKRPSAKDVLKNPIFNKVRGAKEV 495 WD40 repeatMLAPALEMEPVEPQSLKKLSFKSLKRALDLFSPVHGQIAPPDPESKKMRISYSL 117 1580 proteinNFEYGGGSGSEDQVPKRKESGAAQNQGQQAAGASNALALPGPEGSKIPPMEKSQNALTVGPSLRPQGLNDVGLHGKGTAIISASGSSDRNLSTASAIMERLPSRWPRPVWHPPWKNYRVISGHLGWVRSIAFDPSNQWFCTGSADRTIKIWDLASGRLKLTLTGHIEQIRGLAVSSKHTYMFSAGDDKQVKCWDLEQNKVIRSYHGHLSGRLKLTLTPTIDILLTGGRDSVCRVWDIRSKMQIFALSGHDNTVCSVFARPTDPQVVTGSHDTTIKFWDLRHGKTMTTLTNHKKSVRAMAQHPKENCFASASADNIKKFQLPRGEFLHNMLSQQKTIINTMAVNEEGVMATGGDNGSLWFWDWKSGHNGQQAHTIVQPGSLESEAGIYALSYDLTGSRLVSCEADKTIKMWKEDELATPETHPLNFKPPKDIRRF 496 WD40 repeatMEEAAKEQSAGSGKPKLLRYGLRSAAKPKEDKKEEQLHQPPPPPPPQQQAAPAP 111 1700 proteinAPAATRSSTSGSAGGRDRRPQQQHAVDEKYARWKSLVPVLYDWLANHNLLWPSLSCRWGPQLEQATYKNRQRLYISEQTDGSVPNTLVIANCEVVKPRVAAAEHVSQFNEEARSPFIRKYKTIIHPGEVNRIRELPQNPNIVATHTDSPDVLIWDVESQPNRHAVYGATASRPNLILTGHQENAEFALAMCPAEPFVLSGGKDKTVVLWSIQDHITASATDQTTNKSPGSGGSIIKKTGEGNEETGNGPSVGPRGIYCGHEDTVEDVAFCPSTAQEFCSVGDDSCLILWDARIGTNPVAKVEKAHNGDLHCVDWNPHDNNLILTGSADNSVNMFDRRNLTSNGVGSPVYKFEGHKAAVLCVQWSPDKPSVFGSSAEDGLLNIWDYERVDKKVDRAPNAPAGLFFQHAGHRDKIVDFHWNTADPWTMVSVSDDCDTAGGGGTLQIWRMSDLIYRPEEEVLAELENGKAHVLECSKA 497 WD40 repeatMAKDEEEFRGEMEERLVNEEYKIWKKNTPFLYDLVITHALEWPSLTVQWLPDRE 144 1412 proteinEPPGKDYSVQKMILGTHTSDNEPNYLMLAQVQKOKEDAENDARQYDDERGEIGGEGCANGKVQVTQQTNHDGEVNEARYYIPQNPETTATKTVSAEVYVEDYSKHPSKPPQDGGCHPDLRLRGHNTEGYGLSWSPFKHGHLLSGSDDAQICLWDINVPAKNKVLEAQQIFKVHEGVVEDVAWHLRHEYLFGSVGDDRHLLIWDLRTSATNKPLHSVVAHQGEVNCLAFNPFNEWVLATGSADRTVKLFDLRKISSALHTFSCHKEEVFQIGWSPKNETILASCSADRRLMVWDLSRIDEFQTPEDALDGPPELLFIHGGHTSKISDFSWNPCEDWVIASVAEDNILQIWQMAENIYHDEEDDMPPEEVV 498 Cyclin-MGKYMRKGKGVGEVAVMEVSQGSLGVRTRARTLAAASSQKDHRRLGASKSVTTK 793 1683dependant HQSSAPPASPCVESSMHTCYLELRSRKLEKFSRCYHSAHGATSHGESKRSLSLS kinaseEPSRLAVSEEARVASDKSSHRVLQQQSSVAHSRNNASATFSHNAKPAKAAQRKER inhibitorRDDDHTSARPSEAPHEDEDGMEVEASFGENVMDLDSRERRTRETTPSSYTRDVETMETPGSTTRPPSNAGRRRFQTEGGHGTRNQFHVPTTNEIEEFFAGAEQQEQRRFTDRYNYDPVSDSPLPGRFEWVRLRP 499 CDK type DMQNMEENVQSSWSLHGNKEICARYEILKRVSSGTYLDVYRGRRKEDGLIVALKE 415 2196VHDYQSSWREIEALQRLCGCPNVVRLYEVILEFLTSDLYSVIKSAKKNKGENGIPEAEVKAWMIQILQGLANCHANWVIHRDLKPSNMLISAYGILKLADFGSMSFLKRAIYEVEYELPQEDILADAPGERLMDEDDSVKGVWNEGEEDSSTAVETNFDDMAETANLDLSWKNEGDMVMQGFTSGVGTRWYRAPDFLYGATIYGKEIDLWSLGCILGELLILEPLFSGTSNIDOLSRLVKVLGLQQKKNWPGCSNLPDYRKLCFPGDGSPVGLKNHVPNCSDNMFSILERLVCYDPAARLNAKEIVENKYFVEDPYPVLTHELRVPSPLREENNFSEDWAKWKDMEVDSDLENIDEFNVVHSSDGFCIKFS 500 HistoneMAPVKRIEPEKTKANEGKPKRRKVAFAIDTGIEANDCISLHLVSTPEEMRDAEG 109 1653acetyltransferase VEDQSLSFNPEYMQHFVGEHGKIYGYKGLKIDVWLNALSFHAYVDIQYESKVEEGKSEKEATDLTDIMKRIFGRGLVEDRNAFIQSFSSNSQSIESMIHNEGERIATREILTDKGLSAQGDSERLGVSNEIFRLELSDPQIREWHARLEPLVLLFVEGSQPIEQDDPKWEMYIRVQRESLSGGSAVCRLLGFCTVYRFYHYPDTTRLRISQILVFPPYQGKGHGLLLLEAVNKTAVSRDSYDVTVEEPSESLQELRDCMDTIRISQILVFPMPAVKSAVQKLKEANPSDKGAADHCLEGNVNNETVTTSSTKPKNKSGWFPPPGLVEEVRKHLKISKKQFKRCWEILLYLNLDRSDSQCEDKYHISLMEQIMSELFDKSSEKSAKGKRVIDIDNEYDNSKTFIMVRTRNPGNGEGFLPEALEGGMEVSQEDQLKSLFEERLEEIAQIAEKVPSLCKALQMP 501 HistoneMPEDRKKILEALAAKRKAEAESGEKKPRQKSSLNPAKPVSKPVSKPVGGIGSKG 343 1023deacetylase KSTSAPISSTKAKSKHKEEVKAKRVTKMDRYETDEDDESEEEEDLDSESDDDELSDEDSEDDIKSKSVKKLPPQSKGKAPVKGISSSNGKGRDEKGKGIMKDKGKAKAKVEESSSDAEGDSDDDGGDLSDDPLQEVDPSNILPSKTRREASQPTNYQFANMS GDDDDDDDSD 502Histone MADVPESLQQEKDEQGTDKNCCDGKFQKEIDIDDMEEEYNESSIDDEEENLSDN 417 2351deacetylase VATNNMGTIPQGQACMAVTVEGIEHANSVGCGRNGREGSEEVTAAEDMGHVSIENIREQGRNRKSSEQLLALYEQEGLLEDDEDDDDVDWEPFEGVTVQMKWYCTNCTMANSDDSVHCDSCGEHRNSDILRQGFLASPYLPAESPSSSDVPDERLEESKCVMTTLTPSISPMIGVCCSSLQSERRTVVGFDERMLLHSEIQMETYPHPERPDRLRAIAASLRAAGLFPGKCFSIPAREATCEELQTIHSLEHVNAVESTSCGMLSHLSPDTYANEHSSLAARLAAGLCADLAKAIMTGQAQNGFALVRPPGHHAGVKDSMGFCLHNNAAIAVSASRVVGAKKVLIVDWDVHHGNGTQEIFEADQSVLYISLHRHGEGFYPGSGAVTEVGSSKGEGYSVNIPWKCGGVGDNDYIFAFQHAVLPIAEQFEPDLTIISAGFDAAKGDPLGRCEVTPDGFAHMAQMLSCLSKGKMLVILEGGYNLRSISASATAVIKVLLGDNPKALPIDIQPSKGGLQTLLEVFEIQSKYWSSLKGHDQKLRSQWEAQYGSKKRKVIRKRHMHIVGGPVWWKWGRKRVVYYHWFARVSSRKHL 503 PeptidylprolylMASGAGAAGVVEWHQKPPNPKNPVVFFDVTIGTIPAGRIKMELFADIVPRTAEN 69 641 isomeraseFRQFCTGEYRKAGIPIGYKGCHFHRVIKDFMIQAGDFVKGDGSGCISIYGSKFEDENFIAKHTGPGLLSMANSGPNTNGCQFFLTCAKCDWLDNKHVVFGRVLGEGLLVLRKIENVQTGQHNRPKLPCVIAECGEM 504 PeptidylprolylMAKLVSSVCAFSCQQRHPHSRPRFLSNRDHYNHYHNHSHYHNVCYFPPMMMMQQ 172 1623isomerase QLQKQKRMTTKTITSLFKCNSSNHTLLKGLKEFMGFKFRLQAAMLSCEMSILGRVFAIFFIVHQAAAPFPFNHFDNWLVPPASAVLYSPNTKVPRTGEVALRKSIPANPAMKSIQDFLEDIYYLLRFPQRKPYGTMEGDVKSALQIAINEKDSILGSVPLDMKERGLQLYNFLIDGQGGLQVLIEYIKEKDPDKVSVNLSSSLDTIAQLELLQAPGLPYLLPEEYQQYPRLNGRATIEFTMEKGDNSMFSVSSGGGLQKTATIQVVLDGYSAPLTAGNFTKLVIDGAYNGLKLKTTEQAVISDNERAEAGFNLPIEILPAGGFEPLYRTTLSVQDGELPVLPLSVYGAIAMAHNTISEDYSSPSQFFFYLYDKRNAGLGGLSFDEGQFSVFGYTTVGKEILPQLKTGDIIKSAKLVDGFDHLVLPSSST 505 WD40 repeatMDHYYQDDFDYLVDDEMVDFADDVEDDVRTRRRSDIDSDSENDFDSNNKSPDTT 231 1768 proteinALQAKRGKDIQGIPWNRLNFTREKYRETRLQQYKNYENLPRPRRSRNLDKECTNFERGSSFYDFRHNTRSVKATIVHFQLRNLVWATSKHNVYLMQNYSIMHWSSLKQKGEEVLNVAGPIIPSVKHPGSSPQGLTRVQVSAMSVKDNLVVAGGFQGELICKYLDKPGVSFCTKISHDENGITNAVEIYNDASGATRLMTANNDLAVRVFDTEKFTVLERFSFPWSVNHTSVSPDGKLVAVLGDNADCLLADCKTGKTVGTLRGHLDYSFAAAWHPDGYILATGNQDTTCRLWDVRKLSSSLAVLKGRMGAIRSIRFSSDGRFMAMAEPADFVHLYDTRQNYTKSQEIDLFGEIAGISFSPDTEAFFVGVADRTYGSLL EFNRRRMNYYLDSIL506 WD40 repeat MDCSGDEEEEQFFESLEEMLSPSDSGSEAADNETGCRNADARSKYEIWKRAPSS376 2943 protein IQERRQRFLVRMGLANPSELGNQVNSTSAESTCSTETANIPNGIERLRENSGAVLRTAGSSGRKTHCKNVINIGLREGSVRSSSSSNGTPDVGEDNGEFGGTIFSRSGGTWECMCKIKNLDSGKEFVVDELGQDGLWNKLREVGTDRQLTMDEFERSLGLSPLVQELMRRESGVAQADCNGVHHHDAEISSSKRRSWLKALKSAAYSMRRPKEDQSNYDSERSGRRSGSFDVPWGKPQWTKVRHYRKRYKEFTALYMGQEIEAHEGSIWTMKFSLDGRYLASAGQDCVIHVREVIESMRTFGADTPDLYASSAYFSMNGLQELVPLSIEDHANKMKRGKIIGSKKSSNSDCIVLPNKVFQLSEEPVCSFHGHLLDVFDLSWSPSQYLLSSSMDKTVRLWKLGHESCLKVFSHNDIVTCIQFNPVDERYFISGSLDGKARIWSIPDRQVVDWSDLREMVTAVCYTPDGQGGLVGSIKGSCRFYNTSGNKLQLENQLNVRSKKKKSSGKKITGFQFAPGGDSQKVLITSADSRVRVYNGSELVCKYKGFRNTCSQISASFAPNGQHFVCASEDSRVYIWNHESPRGSGARHEKSSWSHEHFLSQGVSVAIPWSGMKLQPPVWNSPEFMLGQRHNLLSLQGGKDVGCQNGLLSREAGEGQESETPLHYISQVSHSCGSQNMVDRDGQDDLSRYSACISDSRLSSFMAFPESPGNPDDLNSKVFFSDSSSKGSATWPEEKLPPTRKQSRSNSTSSHYDTLKTHLGNTIQGQSGASAAVAWGLVIVTAGHGGEIRSFQNYGLPVRL 507 WD40 repeatMPSIPAIGEFTVCEINRELLTTKDESDTQAKDAYAKILGLVFPPISFQIEEGFG 107 1498 proteinSASRQQFDQDLDREDTIVTPSTSEGTNALQEGGLLLKGVSVLKNILASSFGPIFSPNDTKVLKKVELLQGISWHRHKHILAFISGSNQVTVHDFQDPEWRESSLLVSESQRGIEALEWRPNGGTTLSVACRGGICIWSASYPGSVAPVRSGVASFLGTSTRGSSVRWTLVDFLQIPGGKAVTALSWSPTGRLLASASREDSSFTIWDVAQGVGTPLRRGLGGISLLKWSPTGDYLFSAKPNGTFYLWETNTWTLEQWSSSGGCVISATWGPDGRMLFMAFSESTTLGSLHFAGRPPSLDAHLLPMELPEIGSITGGFGNIEKMAWDGCGERLAVSYTGGDLMYVGLIAIYDTRRTPFISASLVGFIRGPGEQVKPLAFAFHDKFKQGPLLSVCWSSGLCCTYPLIFRAH 508 WD40 repeatMEEENAKHTEETRQVQVRFTTKLQPALRVPTTSIAIPAHLTRYGLSDIVNTLLG 118 1425 proteinNDKPQPFDFLVESELVRTSLEKLLLIKGISAEKILNIEYILAVVPPKQEEPSLHDDWVSVVDGSYPNFIFSGSFDSIGRIWKGEGLCTHVLEGHRDAITSAAFIMPSDSSDSFINLATASKDRTLRLWQFKPNEHMTNGKMVRPYKLLKGHTSSVQTVSACPRRNLICSGSWDCSIKIWQTAGEMDIESNAGSVKKRKLEDSTEQIISQIEASRTLEGHSQCVSSVVWLEKDTIYSASWDHSVRSWDVETGVNSLTVGCRKALHCLSIGGEGSALIAAGGADSVLRIWDPRMPGTFTPILQLSSHKSWITACKWHPKSRHHLISASHDGTLKLWDVRSKVPLTTLEAHKDKVLCADWWKEDCVISGGADSTLQIFSNL NLT 509 WD40repeat MNRLRSKRNHILELRLGQSEPEKEATLASNRSRGTNAPIVVEDDDDVVVSSPRS 186 797protein FALARSSVSQRSSRIPIVNEEDLELRLGLAVTGRTSAEHNPRRRHGRVPPNKPIVLCDDAGEADQSSSKKRRTGQQLSSDVQSDESKEVKLTCAICISTMEEETSTICGHIFCKKCITNAIHRWKRCPTCRKKLAINNIHRIYISSSTG 510 WD40 repeatMEEPPPPAVLPSSEDTSIVSSHSFVNAPPTVPVGLDASIPQISTPGINQPGLTI 387 2456 proteinPVPPEAAPLTASLVAASAGMPPAVVPSFVRPAIVAHPSVMPPPSMPLAALPMPVASAVPVAAPHFPPSTPNDNSITPSMPVPTPIVASSSVPPSVTIPGIAPLPFIAPIPVPSSRPVAPSPFMPPARPLGASVSVAMDVDNTDEQDQDADNKGESPSSSPDHPEDPSAAEYEITEESRKVRERQEQAIQELLLRRRAYALAVPTNDSSVRARLRRLNEPITLFGEREMERRDRLRALMAKLDAEGQLEKLMKVQEEEEAAANVDAEEVQEMEGPQVYPFYTEGSQELLKARTEITKFSLPRAVSRLQRARRKREDPDEDEDEELKCVLQQSAQINMDCSEIGDDRPLSGCAFSSDGTLLATSAWSGVTKLWSVPNINKVATLKGHTERVTDVAFSPTNCHLATACADRTAMLWNSEGVLMKTYEGHLDRLARLAFHPSGLYLGTASFDKTWRLWDVNTGIELLLQEGHSRSVYGIAFQCDGSLAATCGLDGLARIWDLRTGRSILALEGHVKPVLGIDFSPNGYHLATGSEDHTCRIWDLRKRQSVYIIPAHSHLVSQVKFEPQEGYFLVTASYDSTAKVWSARDFKSIKVLAGHEAKVTSVDITADGQYIATVSHDRTIKLWSSKNSTNDMNIG 511 WD40 repeatMKRAYKLQEFVAHASNVNCLKIGKKSSRVLVTGGEDHKVNMWAIGKPNAILSLS 359 2761 proteinGHSSAVESVTFDSAEALVVAGAASGTIKLWDLEEAKIVRTLTGHRSNCISVDFHPFGEFFASGSLDTNLKIWDIRRKGCIHTYKGHTRGVNSIRFSPDGRWVVSGGEDNIVKLWDLTAGKLMHDFKCHEGQIQCMDFHPQEFLLATGSADRTVKFWDLETFELIGSAGPETTGVRAMIFNPDGRTLLTGLHESLKVFSWEPLRCYDAVDVGWSKLADLNIHEGKLLGCSYNQSCVGVWVVDISRVGPYAAGNVSRTNGHNEAKLASSGHPSVQQLDNNLKTNMARLSLSHSTESGIKEPKTTTSLTTTEGLSSTPQRAGIAFSSKNLPASSGPPSYVSTPKKNSTSRVQPTTNFQTLSRPDIVPVIVPRSNSLRPETTSDAKKEMNNFGRVVPSTVSTKSTDVIKSGSNRDESDKIDSINQKRMTGNDKTDLNIARAEQHVSSRLDNTNTSSVVCDGNQPAARWIGAAKFRRNSPVDPVVSPHDRSPTFPWSATDDGVTCQPDRQVTAPELSKRVVEPGRARALVASWETREKALTADTPVLVSGRPPTSPGVDMNSFIPRGSHGTSESDLTVSDDNSAIEELMQQHNAFTSILQARLTKLQVIRRFWQRNDLKGAIDATGKMGDHSVSADVISVLIERSEIFTLDICTVILPLLTRLLQSETDRHLTVAMETLLVLVKTFGDVIRATISATPTIGVDLQAEQRLERCNLCYVELENIKQILVPLIRRGGAVAKSAQELSLALQEV 512 Cyclin BMAGSDENNPGVVGGAHVQEGLRVGAGKMGAGNVQQRRALSNINSNIIGAPPYPC 238 1648AVNKRVLSEKNVNSENDLLNAAHRPITRQFAAQMAYKQQLRPEENKRTTQSVSNPSKSEDCAILDVDDDKMADDFPVPMFVQHTEAMLEEIDRMEEVEMEDVAEEPVTDIDSGDKENQLAVVEYIDDLYMFYQKAEASSCVPPNYMDRQQDINERMRGILIDWLIEVHYKFELMDETLYLTVNLIDRFLAVQPVVKKKLQLVGVTAMLLACKYEEVSVPVVEDLILISDRAYSRKEVLEMERLMVNTLHFNMSVPTPYVFMRRFLKAAQSDKKLELLSFFIIELSLVEYDMLKFPPSLLAASAIYTALSTITRTKQWSTTCEWHTSYSEEQLLECARLMVTFHQRAGSGKLTGVHRKYSTSKFGHAARTEPANFLLDF RL 513 Cyclin-MQAPREGKSAAAIVGMGKYMKKSKAIPRDVSLLEASPRSPSATGVRTRAKTLAS 59 859 dependantRRLRRASQRRPPPPAAAAAAAAPSLDASPCPFSYLQLRSRRLRRPRLAPSPEAR kinaseIDEGPAGSGSRGSRDASCSARTASSSGGVEGEGACVGRGDRGNGGECVRDAAVD inhibitorASYGENDLEIEDRDRSTRESTPCSLIRDSNANTPPGSTTRQQSSCTAHRTQMSILRSIPTSDEMEEFFAYAEQRQQRSFIEKYNFDIVKDRPLPGRFEWVQVIP 514 HistoneMDGHSSHLAAQNRSRGSQTPSPSHSAASASATSSIHLKRKLSAANASAASAAAA 44 1829acetyltransferase AAAAAAAADDHAPPFPPSSISADTRDGALTSNDDLESISARGGGAGDDSDDDSDDEEEDDGDNDGGSSLRTFTAARLENVGPAAARNRKIKAESNATVKVEKEDSAKDGGNGAGVGALGPAATSGAGSGSGTVPKEDAVKIFTENLQASGAYSAREENLKREEEAGRLKFECLSNDGVDDHMVWLIGLKNIFARQLPNMPKEYIVRLVMDRNHKSVMVIRRNLVVGGITYRPYASQKFGEIAFCAIKADEQVKGYGTRLMNHLKQHARDVDGLTHFLTYADNNAVGYFIKQGFTKEIYLDKDRWHGYIKDYDGGILMECKIDPKLPYTDLSTMVRRQRQAIDEKIRELSNCHIVYQGIDFQKRDAGVPQNTIKMEDIPGLREAGWTPDQWGYSRFRGLSDQKRLTFFIRQLLKVLNDHSDAWPFKEPVDAREVPDYYDIIKDPMDLKTMTKRVESEQYYVTLEMFIADVKRMFANARTYNSPDTIYFKIATRLEAHFQSKVQSNLQSGAGKIQQ 515 PeptidylprolylMFNGMMDPELFKLAQEQMNRMSPAELAKIQQQMMSNPELMRMASESMKNMRPED 109 1866isomerase LRQAAEQLKHVRPEEMAEIGEKMANASPEEIAAVRARADAQMTYEINAAKILKKEGNELHSQGRFKDASQKYLRAKNNLKGIPSSEGKNLLLACSLNLMSCYLKTRQYEECIKEGSEALACEEKNLKAFYRRGQAYRELGQLKDAVSDLRKAHEISPDDETIAQVLRDTEESLTKEGGSAPRGVVIEEITEEDETLASVNHESPSEYSEKRHQESEDAHKGPINGDIMGQMTNSESLKALKGDPDAIRSFQNFISNADPTTLAAMGAGNAGEVSPDLIKTASSMIGKMSAEELQKMIQLASSFPGENPYVTRNSDSNSNSFGNGSIPNVSPDMLKTASDMMSKMSPDDLQRMFEMASSSRGKDPSLDANHASSSSGANLAANLNHILGESEPSSSYHIPSSSRNISSSPLSNFPSSPGDMQEQIRNQMKDPAMRQMFTSMMKNMSPEMMANMGKQFGLELSPEDAAKAQEAMSSLSPEMLDKMMRWADRAQRGVETAKKTKNWLLGRPGMILAICMLLLAVILHRLGFIGS 516 WD40 repeatMIAAISWVPRGASKAVPEVAEPPSKEEIEEILKSGVVERSGDSDGEEDDENMDA 212 1815 proteinVASEKADEVSTALSAADALGRISKVTKAGSGFEDIADGLRELDMDNYDEEDEDVKLFSTGLGDLYYPSNDMDPYLKDKDDDDDTEEIEDLSIKPMDSLIVCARTDDEVNLLEVYLLEPSLSDESNMYVHHEVVISEFPLCTAWLDCPIKGGDKGNFIAVGSMEPAIEIWDLDIIDAVEPCLVLGGQEELKKKKKKGKKASIKYKEGSHTDSVLGLAWNKEFRNILASASADRQVKIWDVAAGKCNITMEHHTDKVQAVAWNHHAPQVLLSGSFDHSVVMKDGRIPSHSGYRWSVTADVESLAWDPHSEHFFVVSLEDGTVRGFDVRAAISNSASQSLPSFTLHAHEKAVSTISYNPAAPNLLATGSTDKMVKLWDLSNNQPSCIASRNPKAGAVFSVSFSEDSPLLLAIGGSKGRLEVWDTSSDAAVSRRFG KHGKPKTAEPGS 517WD40 repeat MKFCKKYQEYMQGQEGKKLPGLGFKKLKKILKRCRRRDSLHSQKALQAVQNPRT 2071193 protein CPAHCSVCDGSFFPSLLEEMSAVLGCFNKQAQKLLELHLASGFQKYLMWFKGKLRGNHVALIQEGKDLVTYALINAIAIRKILKKYDKIHLSTQGQAFKSQVQRMHMEILQSPWLCELIAFHINVRETKANSGKGHALFEGCSLVVDDGKPSLSCELFDSIKLDIDLTCSICLDTVFDSVSLTCGHIYCYMCACSAASVTIVDGLKAAEPKEKCPLCREARVFEGAVHLDELNILLSRSCPEYWAERLQTERVERVRQAKEHWESQCRAF MGVE 518 WD40repeat MVSTQSTRENPSIFFPPPLKPWLLPVVLSLSLSRQLGMAAAAAASLPFKKNYRS 6 2786protein SQALQQFYAGGPFAVSSDGSFIACNCGDSIKIVDSSNASLRPSIDCGSDTITALSLSPDGKLLFSAGHSRQIRVWDLSTSTCLRSWKGHDGPVMSMACPVSGGLLATGGADRKVMVWDVDGGFCTHFFKGHDGVVSTVLFHPDSNRSLLFSGSDDGTIRVWDLLAKKCASTLRGHDSTVTSLAFSEDGLTLLAAGRDKVVSLWDLHNYACKKTIPMYEVLESVCVIHSGTVLASQLGLDDQLKVTKESAQNIHFITVGERGILRIWKSEGSVCLFKQEHSDVTVISDEDDSRSGFTAAVMLPLDQGLLCVTADQQFLFYYPEKHPEGIFSLTLCRRLVGYNEEIVDMKFLGEEENFLAVATNLEQVRVYELASMSCSYVLAGHTETVLCLDTCISSSGRTLIVTGSKDNSVRLWDSESRHCIGVGVGHMGAVGAVAFSRKRQDFFVSGSSDRTLKVWSLDGISEDGVDSTNLKAKAVVAAHDKDINSVAVAPNDSLVCSGSQDRTACVWRLPDLVSVVVLKGHKRGIWSVEFSPVDQCVLTASGDKTVKIWAISDGSCLKTFEGHVSSVLRASFLTRGTQFVSCGADGLVKLWTVRTNECIATYDQHSDKVWALAVGKKTEMLATGGSDAVVNLWYDSTASDKEDAFRKEEEGVLKGQELENAVSDADYTKAIELALELRRPHKLFELFSELCRTREVGDRVERILSALSGEEVCLLLEYIREWNAKPKLCHVAQSVLSQVFRILSPTEIVEIKGIGELLEGLIPYSQRHFSRIDRLVRSTYLLDYTLTGMSVIEPEADRSAVNDGSPDKSGLEKLEDGLLGENVGEEKIQNKEELESSAYKKRKLPRSKDRSKKKSKNVVYAD AAAISFRA 519 WD40repeat MDSAPRRKSGGINLPSGMSETSLRLDGFSGSSSSFRAISNLTSPSKSSSISDRF 213 1726protein IPCRSSSRLHTFGLVERGSPVKEGGNEAYSRLLKAELFGSDFGSLSPAGQGSPMSPSKNMLRFKTESSGPNSPFSPSILRQDSGFSSEASTPPKPPRKVPKTPHKVLDAPSLQDDFYLNLVDWSSQNTLAVGLGTCVYLWSASNSKVTKLCDLGPNDGVCAVQWTREGSYISIGTSLGQVQIWDGTQCKRVRTMGGHQTRTGVLAWNSRILASGSRDRVILQHDLRVPNEFIGKLVGHKSEVCGLKWSHDDRELASGGNDNQLLVWNQHSQQPVLKLTEHTAAVKAIAWSPHQNGLLASGGGTADRCIRFWNTTNGHQTSSVDTGSQVCNLAWSKNVNELVSTHGYSQNQIMVWKYPSMAKVATLTGHSLRVLYLAMSPDGQTIVTGAGDETLRFWNVFPSAKAPAPVKDTGLWSLGRTHIR 520 WD40 repeatMEDEAEIYDGVRAQFPLTFGKQSKPQTSLESVHSATRRGGPAPAPAPASSSSLP 101 2110 proteinSTTSPSAAGGAGKSSGLPSLSSSSTAWLEGLRAGNPRAGREAGIGSRGGDGEDGGRAMIGPPRPPPGFSANDDGGGEDDDDDGDGVMVGPPPPPPGNLGDGDDDEEEEEAMIGPPRPPVVDSDEEEEEEEEENRYRLPLSNEIVLKGHNKIVSALAVDPTGSRVLSGSYDYTVRMFDFQSMNSRLSSFRDFEPVEGHQVRNLSWSPTADRFLCVTGSAQAKIYDRDGLTLGEFVKGDMYIRDLKNTKGHITGLTWGEWHPKTKETILTSSEDGSLRIWDVNDFKSQKQVIKPKLARPGRVPVTTCTWDREGKCIAGGIGDGSIQIWNLKPGWGSRPDIHVEQAHADDITGLKFSSDGKILLTRSFDDSLKVWDLRLMKNPLKVFEDLPNHYAQTNIACSPDEQLFLTGTSVERESTIGGLLCFFDRSKLELVSRIGISPTCSVVQCAWHPRLNQIFATSGDKSQGGTHVLYDPTLSERGALVCVARAPRKKSVDDFELKPVIHNPHALPLFRDQPSRKRQREKILKDPLKSHKPELPMNGPGHGGRVGASKGSLLTQYLLKQGGMIKETWMDEDPREAILKHADAAEKNPKFTRAYAETQPDPVFAKSDSEDEDK

TABLE 16 BLAST Sequence Alignment Table. BlastX top BlastX e BlastXBlastX SEQ ID Target Patent Identifier hit Gene name value identitiesoverlap 1 CDK type A eucalyptusSpp_003910 Q9FRN5 PUTATIVE 0 367 492SERINE/THREONINE KINASE 2 CDK type A eucalyptusSpp_019213 O44000CDC2-LIKE e−160 217 290 PROTEIN KINASE TPK2 3 CDK type AeucalyptusSpp_036800 Q40789 PROTEIN 0 259 294 KINASE P34CDC2 4 CDK typeA eucalyptusSpp_040260 Q27168 CDC2 e−156 208 304 5 CDK type AeucalyptusSpp_041965 Q43361 CDC2PA mRNA. e−159 274 294 SPTREMBL 6 CDKtype B-1 eucalyptusSpp_002906 Q9FYT9 Cyclin- e−159 269 305 dependentkinase B1-1 7 CDK type B-2 eucalyptusSpp_001518 Q9FSH4 B2-TYPE 0 270 315CYCLIN DEPENDENT KINASE 8 CDK type C eucalyptusSpp_008078 Q9LDC1 CRK1protein 0 415 558 9 CDK type C eucalyptusSpp_009826 Q9LNN0 F8L10.9 0 392716 protein. SPTREMBL 10 CDK type C eucalyptusSpp_010364 Q8GZA7 Putativee−172 309 499 cyclin- dependent protein kinase. 11 CDK type CeucalyptusSpp_011523 Q8W2N0 Cyclin- e−165 273 405 dependent kinase CDC2C12 CDK type C eucalyptusSpp_024358 P93320 CDC2MSC 0 448 523 PROTEIN 13CDK type C eucalyptusSpp_039125 O80540 F14J9.26 0 418 743 protein 14 CDKtype D eucalyptusSpp_005362 O80345 CDK- e−180 305 483 activating kinase1AT (Cdk- activating kinase CAK1At) 15 CDK type D eucalyptusSpp_044857O80345 CDK- e−177 302 477 activating kinase 1AT (Cdk- activating kinaseCAK1At) 16 Cyclin A eucalyptusSpp_001743 Q39879 MITOTIC 0 360 508 CYCLINA2- TYPE 17 Cyclin A eucalyptusSpp_012405 Q39878 MITOTIC e−179 278 470CYCLIN A2- TYPE 18 Cyclin B eucalyptusSpp_003739 Q9LDM4 F2D10.10 e−148288 466 (F5M15.6) 19 Cyclin B eucalyptusSpp_022338 P93557 Mitotic e−168310 476 cyclin 20 Cyclin B eucalyptusSpp_028605 Q40337 B-like e−158 300439 cyclin. SPTREMBL 21 Cyclin B eucalyptusSpp_041006 Q40337 B-likee−158 300 439 cyclin 22 Cyclin D eucalyptusSpp_006643 Q9SXN7 NtcycD3-11E−73 177 404 protein 23 Cyclin D eucalyptusSpp_045338 Q8LK74 CyclinD3.1 e−101 190 332 protein. SPTREMBL 24 Cyclin D eucalyptusSpp_046486Q9ZRX7 CYCLIN D3.2 e−126 196 373 PROTEIN 25 Cyclin- eucalyptusSpp_012070CAB69358 SEQUENCE 1 8E−64 83 88 dependent FROM PATENT kinase WO9841642regulatory subunit 26 Histone eucalyptusSpp_006617 O80378 181 0 371 395acetyltransferase (Fragment) 27 Histone eucalyptusSpp_007827 Q9FJT8Histone e−148 260 465 acetyltransferase acetyltransferase HAT B 28Histone eucalyptusSpp_008036 Q9FJT8 Histone e−149 262 465acetyltransferase acetyltransferase HAT B. SPTREMBL 30 HistoneeucalyptusSpp_001596 Q9M4T5 Putative 7E−76 156 305 deacetylase histonedeacetylase HD2 31 Histone eucalyptusSpp_005870 Q9M4T4 Putative 7E−66144 318 deacetylase histone deacetylase HD2c (AT5g03740/F17C15_160) 32Histone eucalyptusSpp_006901 HDAC_ARATH Histone 0 405 499 deacetylasedeacetylase (HD) 33 Histone eucalyptusSpp_006902 AAM13152 HISTONE 0 427499 deacetylase DEACETYLASE 34 Histone eucalyptusSpp_007440 Q8W508HISTONE 0 369 428 deacetylase DEACETYLASE 35 HistoneeucalyptusSpp_008994 Q8LD93 Histone 0 354 536 deacetylase deacetylase,putative 36 Histone eucalyptusSpp_024580 Q94EJ2 At1g08460/T27G7_7 e−165274 373 deacetylase (HDA8). SPTREMBL 37 Histone eucalyptusSpp_037831Q9FML2 Histone 0 356 464 deacetylase deacetylase. SPTREMBL 38 MAT1 CDK-eucalyptusSpp_034958 Q8LES8 Hypothetical 4E−47 101 190 activatingprotein kinase assembly factor 39 Peptidylprolyl 001209EGXC004488HTTL40_SPIOL Peptidylprolyl 0 329 392 isomerase cis- trans isomerase,chloroplast precursor 40 Peptidylprolyl 010310EGXD012820HT Q9FJL3PEPTIDYLPROLYL 0 453 579 isomerase ISOMERASE 41 Peptidylprolyl010310EGXD013036HT O82646 HYPOTHETICAL 0 302 521 isomerase 57.1 KDAPROTEIN (EC 5.2.1.8) 42 Peptidylprolyl 010316EGXF999037HT BAB39983PUTATIVE e−115 146 172 isomerase PEPTIDYLPROLYL CIS- TRANS ISOMERASE,CHLOROPLAST 43 Peptidylprolyl 010324EGXF002118HT AAK32894AT5G13120/T19L5_80 e−122 179 264 isomerase 44 Peptidylprolyl011019EGKA001923HT AAM14253 HYPOTHETICAL e−108 146 188 isomerase 20.3KDA PROTEIN 45 Peptidylprolyl eucalyptusSpp_000966 Q8L5T1 Peptidylprolyl1E−91 155 170 isomerase isomerase (Cyclophilin) (EC 5.2.1.8) 46Peptidylprolyl eucalyptusSpp_001037 Q8VX73 CYCLOPHILIN e−120 155 169isomerase (EC 5.2.1.8) 47 Peptidylprolyl eucalyptusSpp_004603 AAM14253HYPOTHETICAL e−108 146 188 isomerase 20.3 KDA PROTEIN. 48 PeptidylprolyleucalyptusSpp_005465 Q9SP02 Cyclophilin 2E−93 172 204 isomerase ROC7 (EC5.2.1.8) (AT5g58710/mzn1_160) (Pepti . . . 49 PeptidylprolyleucalyptusSpp_006571 O49605 EC 5.2.1.8 9E−98 169 224 isomerase(Cyclophilin- like protein) (Peptidyl- prolyl 50 PeptidylprolyleucalyptusSpp_006786 Q93VG0 Cyclophilin 5E−82 142 164 isomerase (EC5.2.1.8) (Peptidyl- prolyl cis- trans 51 PeptidylprolyleucalyptusSpp_007057 Q38901 Cytosolic 3E−84 144 172 isomerasecyclophilin (EC 5.2.1.8) (Peptidyl- prolyl 52 PeptidylprolyleucalyptusSpp_008670 Q9FJL3 PEPTIDYLPROLYL 0 423 596 isomerase ISOMERASE53 Peptidylprolyl eucalyptusSpp_009137 Q9C566 Cyclophilin- e−168 285 361isomerase 40 (EC 5.2.1.8) (Expressed protein) 54 PeptidylprolyleucalyptusSpp_010285 Q9LY75 Cyclophylin- e−160 345 658 isomerase likeprotein (EC 5.2.1.8) (Peptidyl- prolyl 55 PeptidylprolyleucalyptusSpp_010600 Q93YQ8 HYPOTHETICAL 0 346 475 isomerase 50.1 KDAPROTEIN (FRAGMENT) 56 Peptidylprolyl eucalyptusSpp_011551 Q9ZVG4T2P11.13 e−115 154 192 isomerase PROTEIN 57 PeptidylprolyleucalyptusSpp_020743 Q8VXA5 PUTATIVE e−125 161 172 isomerase CYCLOSPORINA-BINDING PROTEIN 58 Peptidylprolyl eucalyptusSpp_023739 FK21_NEUCRFK506- 3E−49 74 112 isomerase binding protein precursor (FKBP-21) 60Peptidylprolyl eucalyptusSpp_031985 Q8L8W5 Cyclophilin- 1E−82 155 229isomerase like protein (EC 5.2.1.8) (Peptidyl- prolyl 61 PeptidylprolyleucalyptusSpp_032025 Q9LPC7 F22M8.7 1E−45 99 160 isomerase protein (EC5.2.1.8) (Peptidyl- prolyl cis- trans 62 PeptidylprolyleucalyptusSpp_032173 Q8L8W5 Cyclophilin- 4E−83 156 229 isomerase likeprotein (EC 5.2.1.8) (Peptidyl- prolyl 64 RetinoblastomaeucalyptusSpp_009143 Q9SLZ4 Retinoblastoma- 0 704 1008 related relatedprotein protein 65 WD40 repeat eucalyptusSpp_000349 AAK49947 TGF-BETA 0291 326 protein RECEPTOR- INTERACTING PROTEIN 1 66 WD40 repeateucalyptusSpp_000575 Q9LW17 WD-40 repeat e−168 282 341 proteinprotein-like (Expressed protein) 67 WD40 repeat eucalyptusSpp_000804GBLP_SOYBN Guanine 0 291 326 protein nucleotide- binding protein betasubunit-like 68 WD40 repeat eucalyptusSpp_000805 GBLP_MEDSA Guaninee−171 291 327 protein nucleotide- binding protein beta 69 WD40 repeateucalyptusSpp_000806 GBLP_MEDSA Guanine e−171 291 327 proteinnucleotide- binding protein beta subunit-like 70 WD40 repeateucalyptusSpp_002248 AAL86002 HYPOTHETICAL 0 261 388 protein 43.8 KDAPROTEIN 71 WD40 repeat eucalyptusSpp_003203 Q9SY00 Putative WD- e−144236 317 protein repeat protein (AT4G02730/T5J8_2) 72 WD40 repeateucalyptusSpp_003209 AAM14986 HYPOTHETICAL e−160 259 302 protein 32.6KDA PROTEIN 73 WD40 repeat eucalyptusSpp_004429 Q9SZQ5 HYPOTHETICAL 0260 322 protein 34.3 KDA PROTEIN 74 WD40 repeat eucalyptusSpp_004607AAC27402 EXPRESSED 0 253 356 protein PROTEIN 75 WD40 repeateucalyptusSpp_004682 AAK00964 HYPOTHETICAL 0 264 313 protein 35.3 KDAPROTEIN 76 WD40 repeat eucalyptusSpp_005786 Q944S2 At2g47790/F17A22.18e−155 264 396 protein (Expressed protein). SPTREMBL 77 WD40 repeateucalyptusSpp_005887 Q94AB4 AT3g13340/MDC11_13 0 332 446 protein 78 WD40repeat eucalyptusSpp_005981 Q8L4X6 WD-repeat 0 315 348 protein proteinGhTTG2. SPTREMBL 79 WD40 repeat eucalyptusSpp_006766 Q8L4M1 Putative WD-e−137 234 369 protein 40 repeat protein 80 WD40 repeateucalyptusSpp_006769 Q9LJC6 RETINOBLASTOMA- 0 372 566 protein BINDINGPROTEIN-LIKE 81 WD40 repeat eucalyptusSpp_006907 Q94C94 Hypothetical 0446 812 protein protein. 82 WD40 repeat eucalyptusSpp_007518 Q93ZN5AT4G00090/F6N15_8 0 311 436 protein 83 WD40 repeat eucalyptusSpp_007717O82266 At2g47990 e−180 327 528 protein protein (Hypothetical 58.9 kDaprotein) 84 WD40 repeat eucalyptusSpp_007718 Q8RWD8 Hypothetical e−173278 350 protein protein. SPTREMBL 85 WD40 repeat eucalyptusSpp_007741Q8LA40 Putative WD- e−158 269 409 protein 40 repeat protein, MSI2 86WD40 repeat eucalyptusSpp_007884 Q9FHY2 Similarity e−149 316 765 proteinto unknown protein 87 WD40 repeat eucalyptusSpp_008258 Q9LHN3EMB|CAB63739.1 0 524 758 protein (AT3G18860/MCB22_3) 88 WD40 repeateucalyptusSpp_008465 Q9FLS2 WD-repeat 0 366 460 protein protein-like 89WD40 repeat eucalyptusSpp_008616 Q9LYK6 Hypothetical e−148 252 321protein protein 90 WD40 repeat eucalyptusSpp_008690 Q9SW94 G PROTEIN 0326 376 protein BETA SUBUNIT 91 WD40 repeat eucalyptusSpp_008708 Q8L862Hypothetical e−167 297 487 protein protein 92 WD40 repeateucalyptusSpp_008850 O22725 F11P17.7 0 402 853 protein protein. SPTREMBL93 WD40 repeat eucalyptusSpp_009072 Q9SAJ0 F23A5.2 (form e−176 288 350protein 2) (mRNA export protein, putative) 94 WD40 repeateucalyptusSpp_009465 Q9FLX9 NOTCHLESS 0 384 475 protein PROTEIN HOMOLOG95 WD40 repeat eucalyptusSpp_009472 Q9SZA4 WD-REPEAT 0 374 457 proteinPROTEIN-LIKE PROTEIN 96 WD40 repeat eucalyptusSpp_009550 Q9FKT5Gb|AAF54217.1 e−167 275 313 protein (Hypothetical protein) 97 WD40repeat eucalyptusSpp_010284 O22466 WD-40 repeat 0 397 423 proteinprotein MSI1 98 WD40 repeat eucalyptusSpp_010595 Q94C94 Hypothetical 0419 789 protein protein 99 WD40 repeat eucalyptusSpp_010657 Q94AH2HYPOTHETICAL 0 243 298 protein 33.1 KDA PROTEIN 100 WD40 repeateucalyptusSpp_012636 Q8L611 Hypothetical 0 756 1133 protein protein 101WD40 repeat eucalyptusSpp_012748 AAD10151 PUTATIVE WD- 0 375 469 protein40 REPEAT PROTEIN, MSI4 102 WD40 repeat eucalyptusSpp_012879 Q8VZY6FERTILIZATION- 0 291 377 protein INDEPENDENT ENDOSPERM PROTEIN 103 WD40repeat eucalyptusSpp_015515 Q8LPI5 Putative WD- 0 360 493 protein repeatprotein. SPTREMBL 104 WD40 repeat eucalyptusSpp_015724 O22607 WD-40repeat 0 395 522 protein protein MSI4 105 WD40 repeateucalyptusSpp_016167 Q93YS7 Putative WD- 0 663 917 protein repeatmembrane protein 106 WD40 repeat eucalyptusSpp_016633 Q9SUY6HYPOTHETICAL e−174 240 384 protein 43.8 KDA PROTEIN 107 WD40 repeateucalyptusSpp_017485 Q8RXC4 Hypothetical 0 650 1348 protein 144.7 kDaprotein 108 WD40 repeat eucalyptusSpp_018007 O94289 WD repeat- e−129 302794 protein containing protein 109 WD40 repeat eucalyptusSpp_020775Q8W403 Sec13p e−150 242 304 protein 110 WD40 repeat eucalyptusSpp_023132AAK52092 WD-40 REPEAT 0 458 515 protein PROTEIN 111 WD40 repeateucalyptusSpp_023569 Q9XIJ3 T10O24.21. 0 404 576 protein SPTREMBL 112WD40 repeat eucalyptusSpp_023611 Q8L4J2 Cleavage e−174 301 438 proteinstimulation factor 50K chain (Cleavage stimulation 113 WD40 repeateucalyptusSpp_024934 Q94AB4 AT3g13340/MDC11_13. 0 343 444 protein WD-repeat protein-like SPTREMBL 114 WD40 repeat eucalyptusSpp_025546 O22212Hypothetical 0 352 566 protein 61.8 kDa Trp-Asp repeats containingprotein 115 WD40 repeat eucalyptusSpp_030134 Q9LVF2 Genomic DNA, 0 677946 protein chromosome 3, P1 clone: MIL23 116 WD40 repeateucalyptusSpp_031787 AAL91206 WD REPEAT 0 264 329 protein PROTEIN-LIKE117 WD40 repeat eucalyptusSpp_034435 Q9SAJ0 F23A5.2(form e−178 290 349protein 2) (mRNA export protein, putative). SPTREMBL 118 WD40 repeateucalyptusSpp_034452 Q94BR4 Hypothetical 0 381 525 protein protein(Putative pre-mRNA splicing factor 119 WD40 repeat eucalyptusSpp_035789P93563 Guanine 3E−88 171 356 protein nucleotide- binding protein betasubunit 120 WD40 repeat eucalyptusSpp_035804 Q9FNN2 WD-repeat 0 356 589protein protein- like. SPTREMBL 121 WD40 repeat eucalyptusSpp_043057Q9LV35 WD40-repeat 0 472 610 protein protein. SPTREMBL 122 WD40 repeateucalyptusSpp_046741 Q93VK1 AT4g28450/F20O9_130 0 363 452 protein 123WD40 repeat eucalyptusSpp_047161 Q9ZUN8 Putative WD- 0 350 473 protein40 repeat protein 124 CDK type A pinusRadiata_001766 Q9M3W7 PUTATIVEe−128 237 436 CDC2-RELATED PROTEIN KINASE CRK2.459 e−128 125 CDK type ApinusRadiata_002927 Q9FRN5 PUTATIVE 0 349 470 SERINE/THREONINE KINASE126 CDK type B-1 990309PRCA009171HT Q9FYT8 Cyclin- e−145 244 303dependent kinase B1-2 127 CDK type B-1 pinusRadiata_013714 Q9FYT8CYCLIN- e−174 222 304 DEPENDENT KINASE B1-2 128 CDK type B-1pinusRadiata_016332 Q9FYT8 CYCLIN- e−178 228 304 DEPENDENT KINASE B1-2129 CDK type B-1 pinusRadiata_021677 Q9FYT8 CYCLIN- e−176 229 304DEPENDENT KINASE B1-2 130 CDK type B-1 pinusRadiata_027562 Q9FYT8Cyclin- e−118 211 304 dependent kinase B1-2 131 CDK type CpinusRadiata_001504 Q9LNN0 F8L10.9 0 434 790 protein 132 CDK type CpinusRadiata_015211 Q9LNN0 F8L10.9 0 371 746 protein 133 CDK type CpinusRadiata_020421 P93320 Cdc2MsC 0 318 432 protein 134 CDK type DpinusRadiata_003187 O80345 CDK- e−137 226 485 ACTIVATING KINASE 1AT(CDK- ACTIVATING KINASE CAK1AT) 135 CDK type D pinusRadiata_015661Q947K6 CDK- 0 266 407 ACTIVATING KINASE. 136 Cyclin ApinusRadiata_013874 Q96226 Cyclin e−108 223 474 137 Cyclin ApinusRadiata_014615 CAC27333 PUTATIVE A- 0 332 390 LIKE CYCLIN(FRAGMENT) 138 Cyclin B pinusRadiata_004578 O65064 Probable 9E−87 162217 G2/mitotic- specific cyclin (Fragment) 139 Cyclin BpinusRadiata_023387 O04389 B-like 2E−98 220 466 cyclin 140 Cyclin DpinusRadiata_006970 P93103 CYCLIN-D 1E−75 135 293 LIKE PROTEIN 141Cyclin D pinusRadiata_010322 CAC17049 SEQUENCE 33 e−131 171 254 FROMPATENT WO0065040 142 Cyclin D pinusRadiata_022721 P93103 CYCLIN-D 1E−76137 289 LIKE PROTEIN 143 Cyclin D pinusRadiata_023407 Q9SMD5 CYCD3,28E−90 139 278 PROTEIN 144 Cyclin- pinusRadiata_001945 Q947Y1 PUTATIVE5E−55 74 86 dependent CYCLIN- kinase DEPENDENT regulatory KINASE subunitREGULATORY SUBUNIT 145 Cyclin- pinusRadiata_008233 CAB69358 SEQUENCE 14E−49 65 86 dependent FROM PATENT kinase WO9841642 regulatory subunit146 Cyclin- pinusRadiata_008234 CAB69358 SEQUENCE 1 4E−49 65 86dependent FROM PATENT kinase WO9841642 regulatory subunit 147 Cyclin-pinusRadiata_022054 CAB69358 SEQUENCE 1 8E−55 70 82 dependent FROMPATENT kinase WO9841642 regulatory subunit 148 HistonepinusRadiata_012137 Q9FK40 Histone 0 496 555 acetyltransferaseacetyltransferase (AT5g50320/MXI22_3) 149 Histone pinusRadiata_012582O80378 181 0 354 402 acetyltransferase (Fragment) SPTREMBL 150 HistonepinusRadiata_015285 O80378 181 0 342 401 acetyltransferase (Fragment)151 Histone pinusRadiata_017229 Q9LNC4 F9P14.9 e−118 268 585acetyltransferase protein 152 Histone pinusRadiata_020724 Q9AR19 Histonee−177 355 639 acetyltransferase acetyltransferase GCN5 (Expressedprotein) 153 Histone pinusRadiata_004555 AAM13152 HISTONE 0 331 488deacetylase DEACETYLASE 154 Histone pinusRadiata_004556 AAM13152 HISTONE0 331 488 deacetylase DEACETYLASE 155 Histone pinusRadiata_005729 Q9M4U5Histone 9E−62 154 348 deacetylase deacetylase 2 isoform b 156 HistonepinusRadiata_007395 AAM13152 HISTONE 0 335 426 deacetylase DEACETYLASE157 Histone pinusRadiata_009503 Q8W508 Histone 0 365 427 deacetylasedeacetylase 158 Histone pinusRadiata_011283 AAM19887 AT1G08460/T27G7_7 0255 366 deacetylase 159 Histone pinusRadiata_012322 Q9FML2 HISTONE 0 327435 deacetylase DEACETYLASE (PUTATIVE HISTONE DEACETYLASE) 161 HistonepinusRadiata_023236 Q8RX28 Putative e−144 238 390 deacetylase histonedeacetylase 162 Peptidylprolyl pinusRadiata_000171 Q9FJL3 PEPTIDYLPROLYL0 364 549 isomerase ISOMERASE 163 Peptidylprolyl pinusRadiata_000172Q38949 FK506 0 365 552 isomerase BINDING PROTEIN FKBP62 (ROF1) 164Peptidylprolyl pinusRadiata_001480 Q8VXA5 PUTATIVE e−125 161 172isomerase CYCLOSPORIN A-BINDING PROTEIN 168 PeptidylprolylpinusRadiata_001692 FKB7_WHEAT 70 kDa 0 418 553 isomerase peptidylprolylisomerase (EC 5.2.1.8) 169 Peptidylprolyl pinusRadiata_005313 AAB64339FKBP-TYPE 1E−97 135 175 isomerase PEPTIDYL- PROLYL CIS- TRANS ISOMERASE170 Peptidylprolyl pinusRadiata_006362 BAB39983 PUTATIVE 3E−77 129 168isomerase PEPTIDYL- PROLYL CIS- TRANS ISOMERASE, CHLOROPLA . . . 2903e−77 171 Peptidylprolyl pinusRadiata_006493 Q9C835 Hypothetical 2E−62128 235 isomerase 26.4 kDa protein (EC 5.2.1.8) (Peptidyl- prol . . .172 Peptidylprolyl pinusRadiata_006983 AAK96784 CYCLOPHILIN e−103 151204 isomerase 174 Peptidylprolyl pinusRadiata_007665 Q9LDC0 FKBP-likee−138 239 378 isomerase protein (Genomic DNA, chromosome 3, P1 clone:175 Peptidylprolyl pinusRadiata_012196 Q93VG0 Cyclophilin 4E−74 132 160isomerase (EC 5.2.1.8) (Peptidyl- prolyl cis- trans 176 PeptidylprolylpinusRadiata_013382 Q9C588 HYPOTHETICAL 0 288 581 isomerase 60.2 KDAPROTEIN 177 Peptidylprolyl pinusRadiata_016461 O04287 IMMUNOPHILIN 9E−6688 109 isomerase 178 Peptidylprolyl pinusRadiata_017611 Q9C566Cyclophilin- e−163 276 360 isomerase 40 (EC 5.2.1.8) (Expressed protein)179 Peptidylprolyl pinusRadiata_019776 AAM14253 HYPOTHETICAL e−110 146190 isomerase 20.3 KDA PROTEIN 180 Peptidylprolyl pinusRadiata_020659AAO63961 Hypothetical 7E−85 159 227 isomerase protein SPTREMBL 181Peptidylprolyl pinusRadiata_022559 AAK43974 PUTATIVE 2E−73 113 153isomerase PEPTIDYL- PROLYL CIS- TRANS ISOMERASE 182 PeptidylprolylpinusRadiata_024188 Q9P3X9 PEPTIDYL- e−122 210 379 isomerase PROLYL CIS-TRANS ISOMERASE (EC 5.2.1.8) 183 Peptidylprolyl pinusRadiata_027973Q9SR70 T22K18.11 3E−69 125 171 isomerase protein (AT3g10060/T22K18_11)184 WD40 repeat pinusRadiata_001353 Q9FNN2 WD-repeat 0 317 590 proteinprotein- likeSPTREMBL 185 WD40 repeat pinusRadiata_001978 PRL1_ARATHPP1/PP2A 0 341 502 protein phosphatases pleiotropic regulator PRL1 186WD40 repeat pinusRadiata_002810 AAK49947 TGF-BETA 0 273 326 proteinRECEPTOR- INTERACTING PROTEIN 1 187 WD40 repeat pinusRadiata_002811AAK49947 TGF-BETA 0 273 326 protein RECEPTOR- INTERACTING PROTEIN 1 188WD40 repeat pinusRadiata_002812 AAM15129 HYPOTHETICAL e−127 225 521protein 58.9 KDA PROTEIN 189 WD40 repeat pinusRadiata_003514 Q9FJ94Similarity e−137 242 445 protein to myosin heavy chain kinaseSPTREMBL190 WD40 repeat pinusRadiata_004104 GBB_ORYSA Guanine 0 294 378 proteinnucleotide- binding protein beta subunit 191 WD40 repeatpinusRadiata_005595 Q9FTT9 PUTATIVE 0 320 459 protein DKFZP564O0463PROTEIN 192 WD40 repeat pinusRadiata_005754 Q94JT6At1g78070/F28K19_28SPTREMBL e−168 294 451 protein 193 WD40 repeatpinusRadiata_006463 GBLP_MEDSA Guanine e−152 261 324 protein nucleotide-binding protein beta subunit-like . . . 538 e−152 194 WD40 repeatpinusRadiata_006665 AAM20553 HYPOTHETICAL 0 655 1169 protein 119.9 KDAPROTEIN. 1229 0.0 195 WD40 repeat pinusRadiata_006750 AAM13119HYPOTHETICAL e−158 264 312 protein 35.4 KDA PROTEIN. 560 e−158 196 WD40repeat pinusRadiata_007030 Q9LJN8 MITOTIC e−169 284 335 proteinCHECKPOINT PROTEIN. 595 e−169 197 WD40 repeat pinusRadiata_007854 Q8H919Putative WD 0 429 644 protein domain containing protein 198 WD40 repeatpinusRadiata_007917 AAD10151 PUTATIVE WD- 0 353 462 protein 40 REPEATPROTEIN, MSI4 199 WD40 repeat pinusRadiata_007989 Q9LRZ0 Genomic DNA, 0480 687 protein chromosome 3, TAC clone: K20I9 200 WD40 repeatpinusRadiata_008506 MSI1_LYCES WD-40 repeat 0 364 420 protein proteinMSI1 201 WD40 repeat pinusRadiata_008692 Q8W403 Sec13p e−134 218 301protein 202 WD40 repeat pinusRadiata_008693 Q8W403 Sec13p e−137 222 301protein 203 WD40 repeat pinusRadiata_009170 Q9M0V4 U3 snoRNP- e−127 244524 protein associated- like protein. SPTREMBL 204 WD40 repeatpinusRadiata_009408 Q9SAJ0 F23A5.2(FORM e−171 282 350 protein 2). 602e−171 205 WD40 repeat pinusRadiata_009522 Q8RXQ4 Hypothetical e−129 231395 protein 43.8 kDa protein 206 WD40 repeat pinusRadiata_009734AAO27452 Peroxisomal e−142 227 317 protein targeting signal type 2receptor. SPTREMBL 207 WD40 repeat pinusRadiata_009815 AAM20433 CELLCYCLE 0 326 500 protein SWITCH PROTEIN 208 WD40 repeatpinusRadiata_010670 AAN72058 Expressed e−157 264 345 protein protein 209WD40 repeat pinusRadiata_011297 AAM13100 WD REPEAT e−157 262 337 proteinPROTEIN ATAN11 210 WD40 repeat pinusRadiata_013098 AAM13153 HYPOTHETICALe−136 229 352 protein 39.1 KDA PROTEIN. 487 e−136 211 WD40 repeatpinusRadiata_013172 Q8H0T9 Hypothetical 0 437 860 protein protein 212WD40 repeat pinusRadiata_013589 AAK52092 WD-40 REPEAT 0 448 512 proteinPROTEIN 213 WD40 repeat pinusRadiata_013608 AAC27402 EXPRESSED e−141 202358 protein PROTEIN 214 WD40 repeat pinusRadiata_014299 Q9XED5 Cellcycle 0 335 488 protein switch proteinSPTREMBL 215 WD40 repeatpinusRadiata_014498 Q9FH64 WD REPEAT e−152 206 329 protein PROTEIN-LIKE216 WD40 repeat pinusRadiata_014548 Q93ZS6 HYPOTHETICAL 0 505 763protein 82.2 KDA PROTEIN 217 WD40 repeat pinusRadiata_014610 Q9M298Hypothetical 0 450 922 protein 104.7 kDa protein 218 WD40 repeatpinusRadiata_016090 Q9SIY9 Putative WD- 0 442 802 protein 40 repeatproteinSPTREMBL 219 WD40 repeat pinusRadiata_016722 O22826 Putativee−159 257 310 protein splicing factorSPTREMBL 220 WD40 repeatpinusRadiata_016785 AAG60193 PUTATIVE 0 344 464 protein WD40 PROTEIN 221WD40 repeat pinusRadiata_017094 Q9LV35 WD40-REPEAT 0 406 604 proteinPROTEIN 222 WD40 repeat pinusRadiata_017527 Q9AYE4 Hypothetical e−154254 314 protein 35.3 kDa protein 223 WD40 repeat pinusRadiata_017591O80706 F8K4.21 0 905 1218 protein protein 224 WD40 repeatpinusRadiata_017769 Q9XIJ3 T10O24.21 0 446 607 protein 225 WD40 repeatpinusRadiata_018047 Q8VZY6 FERTILIZATION- 0 285 373 protein INDEPENDENTENDOSPERM PROTEIN 226 WD40 repeat pinusRadiata_018414 Q947M8 COPI 0 455638 protein 227 WD40 repeat pinusRadiata_018986 Q9LFE2 WD40-repeat 0 518886 protein protein 228 WD40 repeat pinusRadiata_019479 Q9SZA4 WD-repeate−156 276 454 protein protein-like protein 229 WD40 repeatpinusRadiata_020144 Q8W514 MSI TYPE 0 288 413 proteinNUCLEOSOME/CHROMATIN ASSEMBLY FACTOR C 230 WD40 repeatpinusRadiata_022480 Q8W514 MSI type e−167 287 426 proteinnucleosome/chromatin assembly factor C 231 WD40 repeatpinusRadiata_023079 Q8W514 MSI type e−169 283 397 proteinnucleosome/chromatin assembly factor C. SPTREMBL 232 WD40 repeatpinusRadiata_026739 Q93YS7 Putative WD- 0 591 918 protein repeatmembrane protein. SPTREMBL 233 WD40 repeat pinusRadiata_026951 Q93VS5AT4g18900/F13C5_70 e−163 290 503 protein (Hypothetical protein) 234WEE1-like pinusRadiata_026529 Q9SRY9 F22D16.3 e−122 209 451 proteinPROTEIN 235 WD40 repeat eucalyptusSpp_006366 Q8LF96 PRL1 protein 0 374492 protein 236 WD40 repeat eucalyptusSpp_017378 O22607 WD-40 repeat 0371 453 protein protein MSI4 237 WD40 repeat pinusRadiata_000888 O22466WD-40 repeat 0 364 420 protein protein MSI1 238 Cyclin-pinusRadiata_014166 Q9FKB5 GENOMIC DNA, 5E−42 114 304 dependantCHROMOSOME kinase 5, TAC inhibitor CLONE: K24G6 (CYCLIN- DEPENDENT 239CDK type D pinusRadiata_003189 Q9M5G4 CDK- 8E−21 56 100 activatingkinase 240 Histone pinusRadiata_009356 Q9FJT8 Histone 7E−85 187 510acetyltransferase acetyltransferase HAT B 241 HistonepinusRadiata_000065 Q9LPW6 F13K23.8 5E−18 71 209 deacetylase protein.242 Histone pinusRadiata_014197 Q8GXJ1 Putative e−170 308 519deacetylase histone deacetylase 243 Peptidylprolyl pinusRadiata_009081Q9ZRQ9 Cyclophilin e−106 185 190 isomerase (EC 5.2.1.8) (Peptidyl-prolyl cis- trans 244 Peptidyprolyl pinusRadiata_013417 Q8H4T0 Putativee−140 235 345 isomerase peptidyl- prolycis- trans isomerase protein 245WD40 repeat pinusRadiata_005755 Q9SKW4 F5J5.6. e−143 144 319 protein 246WD40 repeat pinusRadiata_006670 Q9LDG7 WD-40 repeat e−163 393 960protein protein-like (MJK13.13 protein) 247 WD40 repeatpinusRadiata_007027 Q8GWR1 Hypothetical e−157 276 470 protein protein.248 WD40 repeat pinusRadiata_007276 Q9LF27 Hypothetical e−138 235 428protein 47.3 kDa protein 249 WD40 repeat pinusRadiata_007390 Q94AH4PUTATIVE 3E−17 53 158 protein RING ZINC FINGER PROTEIN. 91 3e−17 250WD40 repeat pinusRadiata_012648 O22212 Hypothetical 0 324 561 protein61.8 kDa Trp-Asp repeats containing protein 251 WD40 repeatpinusRadiata_013171 Q8H0T9 Hypothetical 0 437 860 protein protein. 252Cyclin B eucalyptusSpp_045414 Q9LDM4 F2D10.10 e−142 255 423 (F5M15.6)253 Cyclin- eucalyptusSpp_044328 Q9FKB5 GENOMIC DNA, 1E−54 121 260dependant CHROMOSOME kinase 5, TAC inhibitor CLONE: K24G6 (CYCLIN-DEPENDENT 254 Histone eucalyptusSpp_015615 Q9AR19 Histone 0 390 563acetyltransferase acetyltransferase GCN5 (Expressed protein) 255Peptidylprolyl eucalyptusSpp_017239 Q8GWM6 Hypothetical 0 364 591isomerase protein 256 WD40 repeat eucalyptusSpp_018643 Q93VS5AT4g18900/F13C5_70 0 229 327 protein (Hypothetical protein) 257 WD40repeat eucalyptusSpp_019127 Q9SRX9 F22D16.14 e−131 232 337 proteinprotein. SPTREMBL 258 WD40 repeat eucalyptusSpp_022624 Q9LFE2WD40-repeat 0 594 868 protein protein 259 WD40 repeateucalyptusSpp_032424 Q8LPL5 Cell cycle 0 255 327 protein switch protein260 WD40 repeat eucalyptusSpp_037472 Q9SK69 Putative WD- 0 461 677protein 40 repeat protein (AT2G20330/F11A3.12)

1. An isolated polynucleotide comprising a nucleic acid sequence that (i) is selected from the group consisting of SEQ ID NOs: 1-260 and variants thereof, (ii) is selected from the group consisting of SEQ ID NOs: 521-772 and variants thereof, or (iii) encodes the catalytic or substrate-binding domain of a polypeptide selected from of any one of SEQ ID NOs: 261-520, wherein the polynucleotide encodes a polypeptide having the activity of said polypeptide selected from any one of SEQ ID NOs: 261-520. 2.-5. (canceled)
 6. The isolated polynucleotide of claim 1, wherein the variant has a sequence identity that is greater than or equal to 80% to any one of SEQ ID NOs: 1-260 or encodes a protein with an amino acid sequence having a sequence identity that is greater than 60%, 65%, 70%, 75%, 80%, 85% or 90% to any one of SEQ ID NOs: 261-520, and wherein the protein encoded by the polynucleotide possesses the activity of the protein encoded by said any one of SEQ ID NOs: 1-260. 7.-8. (canceled)
 9. A DNA construct comprising at least one polynucleotide of claim 1, operably linked in sense or antisense orientation to a promoter, wherein the promoter is selected from the group consisting of a constitutive promoter, a strong promoter, an inducible promoter, a regulatable promoter, a temporally regulated promoter, and a tissue-preferred promoter. 10.-13. (canceled)
 14. The DNA construct of claim 9, wherein an RNA transcript of the polynucleotide is complementary to a nucleic acid sequence selected from the group consisting of 1-260.
 15. A plant cell, comprising the DNA construct of claim
 9. 16. The plant cell of claim 15, wherein the plant cell is in a transgenic plant, and wherein the phenotype of the plant is different from a plant of the same species which does not comprise the plant cell, wherein the difference in phenotype is in lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation, ratio of root to branch vegetative development, leaf area index, and leaf shape. 17.-20. (canceled)
 21. The transgenic plant of claim 16, wherein the plant is of a species of Eucalyptus or Pinus.
 22. The transgenic plant of claim 16, wherein the plant exhibits one or more traits selected from the group consisting of increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests, enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, and production of novel proteins or peptides, reduced period of juvenility, an increased period of juvenility, propensity to form reaction wood, self-abscising branches, accelerated reproductive development or delayed reproductive development as compared to a plant of the same species that has not been transformed with the DNA construct. 23.-31. (canceled)
 32. A wood obtained from a transgenic tree which has been transformed with the DNA construct of claim
 9. 33. A wood pulp obtained from a transgenic tree which has been transformed with the DNA construct of claim
 9. 34.-36. (canceled)
 37. An isolated polypeptide comprising an amino acid sequence encoded by the isolated polynucleotide of claim
 1. 38.-43. (canceled)
 44. The isolated polynucleotide of claim 1, wherein the polynucleotide comprises fewer than about 100 nucleotide bases.
 45. A method of correlating gene expression in two different samples, comprising: detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260 and conservative variants thereof in a first sample; detecting a level of expression of the one or more genes in a second sample; comparing the level of expression of the one or more genes in the first sample to the level of expression of the one or more genes in the second sample; and correlating a difference in expression level of the one or more genes between the first and second samples.
 46. The method of claim 45, wherein the first sample and the second sample are plant tissues that are from the same or different plant.
 47. The method of claim 4, wherein the first sample and the second sample are (i) from the same plant tissue, (ii) harvested during a different season of the year, and/or (iii) obtained from plants in different stages of development. 48.-50. (canceled)
 51. The method of claim 46 wherein the plant tissue is selected from the group consisting of vascular tissue, apical meristem, vascular cambium, xylem, phloem, root, flower, cone, fruit, and seed.
 52. The method of claim 51, wherein the plant tissues are obtained from at least one of (i) a different type of tissue, (ii) a different stage of development, or (iii) different stages of the cell cycle. 53.-54. (canceled)
 55. The method of claim 51, wherein the plant tissues are from one or more species of Eucalyptus or Pinus.
 56. (canceled)
 57. The method of claim 45, wherein the step of detecting is effected using one or more polynucleotides capable of hybridizing to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260 under standard hybridization conditions.
 58. (canceled)
 59. The method of claim 57, wherein the step of detecting is accomplished by hybridization to a labeled nucleic acid.
 60. (canceled)
 61. The method of claim 57, wherein at least one of polynucleotides hybridizes to a 3′ untranslated region of the nucleic acid sequence.
 62. (canceled)
 63. The method of claim 57, wherein the one or more polynucleotides comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 521-772. 64.-66. (canceled)
 67. The method of claim 45, further comprising, prior to the detecting steps, the step of amplifying at least one of the genes.
 68. The method of claim 45, further comprising, prior to the detecting steps, the step of labeling at least one of the genes with a detectable label.
 69. A combination for detecting expression of one or more genes, comprising two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260 or to an RNA transcript of a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260.
 70. (canceled)
 71. The combination of claim 69, wherein the oligonucleotides each hybridize to different nucleic acid sequences or to different RNA transcripts.
 72. (canceled)
 73. The combination of claim 69, wherein at least one of the oligonucleotides hybridizes to a 3′ untranslated region of a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260. 74.-75. (canceled)
 76. The combination of claim 69, wherein at least one of the oligonucleotides comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 521-772. 77.-83. (canceled)
 84. The combination of claim 69, comprising from about 2 to about 5000 oligonucleotides.
 85. The combination of claim 84, wherein each of the oligonucleotides is labeled with a detectable label.
 86. A microarray comprising the combination of claim 69 provided on a solid support, wherein each of the oligonucleotides occupies a unique location on said solid support.
 87. (canceled)
 88. A method for detecting one or more nucleic acid sequences in a sample, comprising contacting the sample with the combination of claim
 69. 89.-91. (canceled)
 92. The method of claim 88, wherein at least one of the oligonucleotides hybridizes to a 3′ untranslated region of a gene that comprises the nucleic acid sequence of at least any one of SEQ ID NOs 1-260. 93.-103. (canceled)
 104. A kit for detecting gene expression comprising the microarray of claim 86 and one or more buffers or reagents for a nucleotide hybridization reaction. 